Diabetes & Metabolism Journal

Hyuk Sang Kwon (Kwon HS)

23 Articles

Clinical Implications of Serum Biomarkers in Diabetic Cardiovascular Complications.: Jang Won Son, Hyuk Sang Kwon; Korean Diabetes J. 2009;33(5):363-372. Published online October 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.5.363

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Abstract PDF: Diabetes is associated with increased risk of cardiovascular disease, with atherosclerosis responsible for most associated morbidity and mortality. Atherosclerosis often causes acute thrombotic events through plaque rupture and formation of platelet-rich thrombi. The principal clinical manifestations of atherosclerosis are coronary artery disease, ischemic stroke, and peripheral arterial disease. Endothelial dysfunction, oxidative stress, and low-grade inflammation are key features in the pathophysiology of atherosclerosis.

Association of Spot Urine Albumin-to-Creatinine Ratio and 24 Hour-Collected Urine Albumin Excretion Rate in Patients with Type 2 Diabetes Mellitus.: Jee In Lee, Hyuk Sang Kwon, Su Jin Oh, Jung Min Lee, Sang Ah Chang, Bong Yun Cha, Hyun Shik Son, Tae Seo Sohn; Korean Diabetes J. 2009;33(4):299-305. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.299

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Abstract PDF: BACKGROUND
Measuring urine albumin in diabetic patients is an important screening test to identify those individuals at high risk for cardiovascular disease and the progression of kidney disease. Recently, spot urine albumin-to-creatinine ratio (ACR) has replaced 24 hour-collected urine albumin excretion rate (AER) as a screening test for microalbuminuria given its comparative simplicity. The purpose of the current study was to evaluate the degree of correlation between AER and ACR in the normal, microalbuminuric and macroalbuminuric ranges, and to identify the lower limits of ACR for both genders. METHODS: A total of 310 type 2 diabetics admitted to one center were enrolled in the present study. Following the collection of a spot urine sample, urine was collected for 24 hours and albumin content was measured in both specimens. RESULTS: Mean patient age was 60.2 years. A total of 25.4% had microalbuminuria and 15.8% had macroalbuminuria. The data revealed a strongly positive correlation between AER and ACR across all ranges of albuminuria (R = 0.8). The cut-off value of ACR for 30 mg/day of AER by the regression equation was 24 microgram/mg for men, 42 microgram/mg for women and 31.2 microgram/mg for all patients. The diagnostic performance expressed as the area under the curve (AUC) was 0.938 (95% CI, 0.911-0.965) for ACR. ACR revealed a sensitivity of 84% and specificity of 84%, when a cut-off value of 31.2 microgram/mg was employed. CONCLUSION: ACR was highly correlated with AER, particularly in the range of microalbuminuria. The gender combined cut-off value of ACR in type 2 diabetic patients was determined to be 31.2 microg/mg However, additional studies of large outpatient populations, as opposed to the inpatient population used in the present study, are required to confirm the utility of this value.

The Changes of Central Aortic Pulse Wave Analysis in Metabolic Syndrome.: Jee In Lee, Tae Seo Sohn, Hyuk Sang Kwon, Jung Min Lee, Sang Ah Chang, Bong Yun Cha, Hyun Shik Son; Korean Diabetes J. 2008;32(6):522-528. Published online December 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.6.522

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Abstract PDF

The metabolic syndrome (MS) has been characterized as a cluster of risk factors that includes dyslipidemia, hypertension, glucose intolerance and central obesity. This syndrome increases the risk of cardiovascular disease. Augmentation index (AIx), a composite of wave reflection form medium-sized muscular arteries is related to the development of coronary artery disease. The aim of this study is to examine the change on central aortic waveforms in subjects between patients with metabolic syndrome and normal subjects. Using the non-invasive technique of pulse wave analysis by applantation tonometry, we investigated central aortic waveforms in 45 patients with MS and 45 matched controls. The MS was defined by NCEP-ATP III criteria. Age did not differ between the two groups. AIx was significantly elevated in patinets with MS compared with controls (21.91 +/- 11.41% vs 18.14 +/- 11.07%; P < 0.01). Subendocardial viability ratio (SEVR) (158.09 +/- 28.69 vs 167.09 +/- 30.06; P < 0.01) was significantly decreased in patients with MS compared with controls. Only the fasting glucose (r = 0.317, P = 0.03) among the components of MS and age (r = 0.424, P = 0.004) had a positive correlation with AIx. AIx increased as the number of MS components increased. These results show that the MS increased systemic arterial stiffness. Age and fasting blood glucose are independent risk factors of arterial stiffness in MS. The individual MS components, except for fasting blood glucose, do not affect arterial stiffness independently. But the clustering of MS components might interact to synergistically affect arterial stiffness.

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Arterial Stiffness by Aerobic Exercise Is Related with Aerobic Capacity, Physical Activity Energy Expenditure and Total Fat but not with Insulin Sensitivity in Obese Female Patients with Type 2 Diabetes
Ji Yeon Jung, Kyung Wan Min, Hee Jung Ahn, Hwi Ryun Kwon, Jae Hyuk Lee, Kang Seo Park, Kyung Ah Han
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The Changes of the body composition and vascular flexibility According to Pilates mat Exercise during 12 weeks in elderly women
Ji-Eun Jang, Yong-Kwon Yoo, Byung-Hoon Lee
The Journal of the Korea institute of electronic communication sciences.2013; 8(11): 1777. CrossRef
Traditional East Asian Medical Pulse Diagnosis: A Preliminary Physiologic Investigation
Kylie A. O'Brien, Stephen Birch, Estelle Abbas, Paul Movsessian, Michael Hook, Paul A. Komesaroff
The Journal of Alternative and Complementary Medicine.2013; 19(10): 793. CrossRef

Cystatin C is a Valuable Marker for Predicting Future Cardiovascular Diseases in Type 2 Diabetic Patients.: Seung Hwan Lee, Kang Woo Lee, Eun Sook Kim, Ye Ree Park, Hun Sung Kim, Shin Ae Park, Mi Ja Kang, Yu Bai Ahn, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Hyuk Sang Kwon; Korean Diabetes J. 2008;32(6):488-497. Published online December 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.6.488

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BACKGROUND
Recent studies suggest that serum Cystatin C is both a sensitive marker for renal dysfunction and a predictive marker for cardiovascular diseases. We aimed to evaluate the association between Cystatin C and various biomarkers and to find out its utility in estimating risk for cardiovascular diseases in type 2 diabetic patients. METHODS: From June 2006 to March 2008, anthropometric measurements and biochemical studies including biomarkers for risk factors of cardiovascular diseases were done in 520 type 2 diabetic patients. A 10-year risk for coronary heart diseases and stroke was estimated using Framingham risk score and UKPDS risk engine. RESULTS: The independent variables showing statistically significant associations with Cystatin C were age (beta = 0.009, P < 0.0001), hemoglobin (beta = -0.038, P = 0.0006), serum creatinine (beta = 0.719, beta < 0.0001), uric acid (beta = 0.048, P = 0.0004), log hsCRP (beta = 0.035, P = 0.0021) and homocysteine (beta = 0.005, P = 0.0228). The levels of microalbuminuria, carotid intima-media thickness, fibrinogen and lipoprotein (a) also correlated with Cystatin C, although the significance was lost after multivariate adjustment. Calculated risk for coronary heart diseases increased in proportion to Cystatin C quartiles: 3.3 +/- 0.4, 6.2 +/- 0.6, 7.6 +/- 0.7, 8.4 +/- 0.7% from Framingham risk score (P < 0.0001); 13.1 +/- 0.9, 21.2 +/- 1.6, 26.1 +/- 1.7, 35.4 +/- 2.0% from UKPDS risk engine (P < 0.0001) (means +/- SE). CONCLUSIONS: Cystatin C is significantly correlated with various emerging biomarkers for cardiovascular diseases. It was also in accordance with the calculated risk for cardiovascular diseases. These findings verify Cystatin C as a valuable and useful marker for predicting future cardiovascular diseases in type 2 diabetic patients.

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Lack of Association between Serum Cystatin C Levels and Coronary Artery Disease in Diabetic Patients
Eun Hee Kim, Ji Hee Yu, Sang Ah Lee, Eui Young Kim, Won Gu Kim, Seung Hun Lee, Eun Hee Cho, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Ki-Up Lee
Korean Diabetes Journal.2010; 34(2): 95. CrossRef
Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients
Seung-Hwan Lee, Shin-Ae Park, Seung-Hyun Ko, Hyeon-Woo Yim, Yu-Bae Ahn, Kun-Ho Yoon, Bong-Yun Cha, Ho-Young Son, Hyuk-Sang Kwon
Metabolism.2010; 59(2): 241. CrossRef

A Study on Resistance in Type 2 Diabetic Patient Against Commencement of Insulin Treatment.: Sun Hwa Hong, Mi Jin Kim, Sung Gab Noh, Dae Won Suh, Suk Jung Youn, Kwan Woo Lee, Ho Chae Lee, Yang Soo Chung, Hong Ryang Chung, Hyuk Sang Kwon, Bong Yun Cha, Ho Young Son, Kun Ho Yoon; Korean Diabetes J. 2008;32(3):269-279. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.269

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BACKGROUND
To achieve tight glycemic control in the poorly controlled type 2 diabetic patients with oral hypoglycemic agent, it maybe beneficial to initiate insulin treatment at the early stage. Many patients with type 2 diabetes are often reluctant to begin insulin therapy despite poor glycemic control with oral hypoglycemic agents, this little known phenomenon, often termed 'psychological insulin resistance (PIR)'. This study investigates psychological insulin resistance in Korean patients with type 2 diabetes. METHOD: This study examined a total of 76 type 2 diabetic patients with poor glycemic control during period of April to July 2006. Through questionnaire and telephone survey, total 24 questions were asked about various attitudes on insulin therapy including psychological barriers and patients' acceptance of this treatment. Subjects were asked to allocate points in 5-point scale (from 5 points for 'very true' to 1 point for 'very untrue'). RESULTS: The means of psychological rejection, injection-related anxiety and fear of insulin side effects such as hypoglycemia and weight gain were 3.65 +/- 0.92, 3.17 +/- 0.98 and 2.8 +/- 1.02, respectively. Unwillingness was common in insulin therapy, 67% of patient rejected or was unwilling to take insulin. Main reasons of patients most frequently endorsed beginning insulin indicate that disease is worsening, permanence (once you start insulin you can never quit) and sense of personal failure. Furthermore, study indicates that patients' reasons for avoiding insulin therapy were mainly psychological rejection, which extended far beyond a simple injection related anxiety. CONCLUSION: PIR was psychological reluctance rather than injection related anxiety. To overcome these psychological barriers to insulin treatment, it is necessary to address appropriate diabetes education including training and counseling with excellent interactive communications between patients and clinicians.

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Using Motivational Interviewing to Overcome Psychological Insulin Resistance
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Factors influencing psychological insulin resistance in type 2 diabetes patients
Ji Hyeon Yu, Hye Young Kim, Sung Reul Kim, Eun Ko, Heung Yong Jin
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Development of a Psychological Insulin Resistance Scale for Korean Patients with Diabetes
Youngshin Song, Younghee Jeon, Jeonghwa Cho, Bohyun Kim
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Patients' perspectives on taking insulin in diabetes - Perspectives of convergence
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The Effects of Exendin-4 on IRS-2 Expression and Phosphorylation in INS-1 Cells.: Ji Hyun Kim, Ji Won Kim, Sung Yoon Jeon, Heon Seok Park, Dong Sik Ham, Young Hye You, Seung Hwan Lee, Jae Hyoung Cho, Mi Ja Kang, Kang Woo Lee, Hyuk Sang Kwon, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Sung Koo Kang, Ho Young Son; Korean Diabetes J. 2008;32(2):102-111. Published online April 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.2.102

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Abstract PDF: BACKGROUND
Insulin receptor substrate 2 (IRS-2) is a key regulator of beta cell proliferation and apoptosis. This study was aimed to investigate effect of the glucolipotoxicity on apoptosis in INS-1 cell, and the effect of Exendin-4, a GLP-1 receptor agonist, on IRS-2 expression in the glucolipotoxicity induced INS-1 cell. The goal was to discover the new action mechanism and function of Exendin-4 in beta cell apoptosis. METHOD: INS-1 cells were cultured in glucolipotoxic condition for 2, 4 or 6 days and were categorized as G groups. Another group in which 50 nM Exendin-4 was added to INS-1 cells, cultured in glucolipotoxic condition, were named as Ex-4 groups. We investigated the expression of IRS-2 by RT-PCR, phosphorylated IRS-2 and phosphorylated Akt protein levels by western blot. We measured the apoptosis ratio of INS-1 cell in glucolipotoxic condition by TUNEL staining in both groups. RESULT: IRS-2 expression of INS-1 cells decreased with correlation to the time of exposure to glucolipotoxic condition. pIRS-2 and pAkt protein levels decreased in the similar pattern in glucolipotoxicity group. However, this effect of glucolipotoxicity on INS-1 cell was inhibited by the Exendin-4 treatment. In the Ex-4 groups, IRS-2 expression, pIRS-2 and pAkt protein levels remained at the similar level to low glucose condition state. Also, apoptosis induced by glucolipotoxicity was suppressed by Exendin-4 treatment significantly. CONCLUSION: We showed that the long-term treatment of Exendin-4 inhibited the apoptosis of beta cells significantly in glucolipotoxic condition and that this effect of Exendin-4 was related with IRS-2 and Akt among the beta cell's intracellular signal transduction pathway.

AICAR Reversed the Glucolipotoxicity Induced beta-cell Dysfunction through Suppression of PPAR-gamma-coactivator-1 (PGC-1) Overexpression.: Hyuk Sang Kwon, Ji Won Kim, Heon Seok Park, Seung Hyun Ko, Bong Yun Cha, Ho Young Son, Kun Ho Yoon; Korean Diabetes J. 2007;31(4):310-318. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.310

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Abstract PDF: BACKGROUND
Glucolipotoxicity plays an important role in the progression of type 2 diabetes mellitus via inducing insulin secretory dysfunction. Expression of insulin gene in pancreatic beta cell might be regulated by AMP-activated protein kinase (AMPK), which is recognized as a key molecule of energy metabolism. We studied the effects of AMPK on glucolipotoxicity-induced beta-cell dysfunction by suppression of PPAR-gamma-coactivator-1 (PGC-1) in vitro and in vivo. Method: Glucolipotoxicity was induced by 33.3 mM glucose and 0.6 mM (palmitate and oleate) for 3 days in isolated rat islets. Messenger RNA (mRNA) expressions of beta-cell specific gene like insulin, BETA2/NeuroD and PGC-1 induced by glucolipotoxic condition and their changes with 5-aminoimidazole-4-carboxy-amide-1-D-ribofuranoside (AICAR) treatment were investigated using RT-PCR. We also examined glucose stimulated insulin secretion in same conditions. Furthermore, SD rats were submitted to a 90% partial pancreatectomy (Px) and randomized into two groups; Ad-GFP-infected Px rats (n = 3) and Ad-siPGC- 1-infected Px rats (n = 3). Then, the Px rats were infected with Ad-GFP or Ad-siPGC-1 (1 x 10(9) pfu) via celiac artery. After 12 days of viral infection, we measured body weight and performed the intraperitoneal glucose tolerance test (IP-GTT). RESULTS: Glucolipotoxicity resulted in blunting of glucose-stimulated insulin secretion, which was recovered by the AICAR treatment in vitro. Suppression in their expressions of insulin and BETA2/NeuroD gene by glucolipotoxic condition were improved with AICAR treatment. However, PGC-1alpha expression was gradually increased by glucolipotoxicity, and suppressed by AICAR treatment. Overexpression of PGC-1 using an adenoviral vector in freshly isolated rat islets suppressed insulin gene expression. We also confirmed the function of PGC-1 using an Ad-siPGC-1 in vivo. Direct infection of Ad-siPGC-1 in 90% pancreatectomized rats significantly improved glucose tolerance and increased body weight. CONCLUSION: AMPK could protect against glucolipotoxicity induced beta-cell dysfunction and the suppression of PGC-1 gene expression might involved in the insulin regulatory mechanism by AMPK.

The Differences of Circulating Adiponectin Levels and Multimerization According to Obesity in Type 2 Diabetes Mellitus of Men.: Sang Ah Chang, Ho Young Son, Jung Min Lee, Tae Seo Sohn, Hyuk Sang Kwon, Hyun Shik Son, Kun Ho Yoon, Hee Seung Kim, Bong Yun Cha, Kwang Woo Lee; Korean Diabetes J. 2007;31(3):243-252. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.243

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Abstract PDF: BACKGROUND
Adiponectin is adipose tissue derived hormone, which has been shown to play an important role in the regulation of glucose and lipid metabolism. Low adiponectin levels are associated with obesity and diabetes and coronary artery disease. In addition to adiponectin level, the adiponectin multimerization and its ratio to total adiponectin have also affect on metabolic risk factors and insulin resistance. However, the adiponectin multimerization pattern in type 2 diabetes of Korean has not been established. We investigated adiponectin levels and adiponectin multimerization pattern according to obesity in type 2 diabetes males of Korean. METHOD: The subjects of this study were 86 of diabetes patients and 89 of control subjects whose fasting blood glucose was below 110 mg/dL. They were divided into two subgroup, non-obese and obese, according to BMI (non-obese 25 < BMI). Anthropometric parameter and other metabolic risk factors were measured. Insulin resistance was presented by HOMA-IR. Plasma adiponectin level was measured by radioimmunoassay method. Adiponectin multimerization was fractionated by SDS-PAGE under non-reducing and non-heat denaturing state and performed immunoblotting. RESULT: Serum adiponectin levels were significantly reduced in obese than non obese group in diabetes patients (7.73 +/- 5.2 versus 12.56 +/- 8 microgram/mL, P = 0.003). Correlational analyses demonstrated that BMI, body weight, waist circumference, diastolic pressure, glucose and height correlated significantly with adiponectin levels in the diabetes patients. The HOMA-IR did not affect the plasma adiponectin levels in diabetic patients. There were no differences in adiponectin multimerization distribution and ratio between obese and non-obese group in the diabetes, however middle molecular weight multimers (MMW, ~110~160 Kda, hexamer) ratio in the control subjects were significantly reduced in obese group than non-obese group (49 +/- 9 versus 56 +/- 11%, P < 0.05). CONCLUSION: The adipoenctin levels were lower in obese than non-obese group of diabetes males in Korea. Aiponectin levels correlated with BMI and weight but not insulin resistance. The differences of adiponectin multimerization distribution and ratio between obese and non-obese group in diabetes were not detected.

Proliferation and Differentiation of Pancreatic beta Cells in L-type Calcium Channel alpha(1D) Subunit (Ca(v)1.3) Heterozygous Knock Out Mice After Partial Pancreatectomy.: Yoon Hee Choi, Il Hee Yun, Sun Hee Suh, Dong Jun Lim, Jae Hyuung Cho, Hyuk Sang Kwon, Bong Yun Cha, Ho Young Son, Chung Gyu Park, Kun Ho Yoon; Korean Diabetes J. 2007;31(3):208-219. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.208

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Abstract PDF: BACKGROUND
S: L-type voltage-dependent calcium channel (LTCC) plays a crucial role in insulin secretion from pancreatic beta cells through Ca2+ influx. In the recent report, LTCC Ca(v)1.3 subtype homozygous knock out mice showed impairment of postnatal pancreatic beta cell development as well as insulin secretion. METHODS: We performed 90% partial pancreatectomy in heterozygous Ca(v)1.3 knock out mice to investigate the effect of partial deficiency of Ca(v)1.3 gene on beta cell regeneration in the adult. Glucose homeostasis, metabolic profiles including serum insulin and lipid levels and morphologic changes of pancreatic islets were studied. RESULTS: 90% Partial pancreatectomy induced glucose intolerance only in the heterozygous knock out mice at 8 weeks after surgery. Distribution of islet size was significantly different between two groups after partial pancreatectomy; median value of islet size of heterozygote was larger than that of wild type (642.8 micrometer2 vs 1459.8 micrometer2, P < 0.01). The frequency of single beta cell unit, considered as a unit of beta cell neogenesis, was much lower in heterozygote than that of wild type (41% vs 23.3%, P < 0.05). CONCLUSION: These data suggest that Ca(v)1.3 gene deficiency is specifically associated with impairment of beta cell regeneration, especially neogensis and eventual glucose intolerance in the 90% partial pancreatectomized mice.

Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus.: Seung Hyun Ko, Hyuk Sang Kwon, Jung Min Lee, Sung Rae Kim, Jae Hyung Cho, Ki Dong Yoo, Yong Moon Park, Won Chul Lee, Ki Ho Song, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yu Bai Ahn; Korean Diabetes J. 2006;30(3):226-235. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.226

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BACKGROUND
Diabetic autonomic neuropathy has a significant negative impact on survival and quality of life in type 2 diabetic patients. Especially cardiovascular autonomic neuropathy (CAN) is clinically important, because of its correlation to cardiovascular death. Therefore, we investigated the prevalence of CAN in Korean type 2 diabetic patients. METHODS: 1798 type 2 diabetic patients, 727 males and 1071 females, visited Diabetes Clinic at St. Vincent Hospital, Korea, were included from January 2001 to December 2005. Clinical evaluation, laboratory test and assessment of diabetic complication were completed. Standard test for CAN were performed: 1) heart rate variability (HRV) during deep breathing (E/I ratio) 2) Valsalva maneuver 3) 30:15 ratio 4) blood pressure response to standing. CAN score was determined according to the results of the test as following: 0 = normal, 1 = abnormal. RESULTS: Mean age and diabetic duration of patients were 56.7 +/- 10.9, and 9.4 +/- 7.5 years. Normal and abnormal CAN were detected in 815 (45.3%) and 983 (54.7%) of the patients, respectively. Abnormal E/I, valsalva, and 30:15 ratio were found in 333 (18.5%), 717 (39.9%), and 546 (30.4%) patients, respectively. Age, diabetic duration, postprandial hyperglycemia, HbA1c, C-reactive protein, and microalbumuria levels were significantly different between normal and abnormal CAN groups. 49 (6.0%) patients of normal and 100 (10.2%) patients of abnormal CAN group showed previous attack of stroke (P = 0.004). In addition, diabetic foot was more frequent in patients with CAN (normal vs. abnormal, 14 (1.7%) vs. 73 (7.4%), P < 0.05). CONCLUSION: CAN is frequently found in Korean type 2 diabetic patients. It was associated with diabetic duration, uncontrolled diabetes, increased albumin excretion rate, presence of retinopathy, postprandial hyperglycemia.

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Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea
Sol Jae Lee, Su Jin Jeong, Yu Chang Lee, Yong Hoon Lee, Jung Eun Lee, Chong Hwa Kim, Kyung Wan Min, Bong Yun Cha
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Screening of Autonomic Neuropathy in Patients with Type 2 Diabetes
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Clustering Characteristics of Risk Variables of Metabolic Syndrome in Korean Rural Populations.: Yong Moon Park, Hyuk Sang Kwon, Sun Young Lim, Jin Hee Lee, Sung Rae Kim, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yong Gyu Park, Dong Suk Kim, Kwang ho Meng, Won Chul Lee; Korean Diabetes J. 2006;30(3):177-189. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.177

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BACKGROUND
The risks of both type 2 diabetes mellitus and cardiovascular disease are mainly associated with the metabolic syndrome which is characterized by clustering of metabolic risk factors, including abdominal obesity, glucose intolerance, hypertension, and dyslipidemia. This study aimed to examine the relations among metabolic risk variables and the underlying structure of the metabolic syndrome that unites related components. METHODS: Subjects were selected by stratified random cluster sampling among persons aged over 40 years from a rural area. Waist circumference, BMI, fasting glucose, fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and diastolic blood pressure were used as risk variables of metabolic syndrome. Factor analysis, a multivariate correlation statistical technique, was performed on a dataset from nondiabetic 3,443 men and women without history of coronary heart disease. RESULTS: Exploratory factor analysis identified three factors in both gender (obesity, hypertension, and dyslipidemia-insulin resistance in men; obesity-insulin resistance, hypertension, and dyslipidemia in women). Fasting insulin was a common contributor to the structure of metabolic syndrome in male subjects, smokers and alcohol drinking group. Confirmatory factor analysis based on the results of exploratory factor analysis revealed that metabolic syndrome was represented primarily by obesity factor in men, obesity-insulin resistance factor in women, and that dyslipidemia factor was highly correlated with obesity factor in men, with insulin resistance factor in women. CONCLUSION: Underlying structure of metabolic syndrome was different between men and women, and obesity might be a primary target for prevention of both type 2 diabetes mellitus and cardiovascular disease in Korea.

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Disjoint factor analysis with cross-loadings
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Hong-Seok Lee, Yong-Moon Park, Hyuk-Sang Kwon, Jin Hee Lee, Kun-Ho Yoon, Ho Young Son, Dong Suk Kim, Hyeon Woo Yim, Won-Chul Lee
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Optimal Waist Circumference Cutoff Value Reflecting Insulin Resistance as a Diagnostic Criterion of Metabolic Syndrome in a Nondiabetic Korean Population Aged 40 Years and Over: The Chungju Metabolic Disease Cohort (CMC) Study
Yong-Moon Park, Hyuk-Sang Kwon, Sun Young Lim, Jin-Hee Lee, Kun-Ho Yoon, Ho-Young Son, Hyeon Woo Yim, Won-Chul Lee
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Prevalence, Awareness, Treatment, and Control of Hypertension Among People Over 40 Years Old in a Rural Area of South Korea: The Chungju Metabolic Disease Cohort (CMC) Study
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Clinical and Experimental Hypertension.2010; 32(3): 166. CrossRef

Perspectives of "Ubiquitous Health Care System" for Diabetes Management.: Jae Hyoung Cho, Hyuk Sang Kwon, Kun Ho Yoon; Korean Diabetes J. 2006;30(2):87-95. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.87

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Abstract PDF

Although clear evidences of the beneficial effects of tight glycemic control on diabetic patients had been already made, the past decade has not seen any noticeable improvement in terms of glycemic control. "Ubiquitous health care system", which is one of the developing fusion technologies of IT, BT and NT, could give us new solutions in future. We established the Internet based glucose monitoring system (IBGMS) and conducted prospective, randomized short-term and long-term clinical trials using the system which can guide the patients with diabetes by mobile technology anytime and anywhere. The mean HbA1c and HbA1c fluctuation index (SD of mean HbA1c) during the whole study period was significantly lowered by the intervention, suggesting more improved state in both HbA1c level and glucose stability. Appropriate physician's advises to the patients' questions and problems at the right time through the IBGMS were the major interventions. Although many unsolved problems still exist, the Internet-based bidirectional communication system developed by the advanced information technology can contribute to the foundations to tomorrow's or ubiquitous medicine

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Sung Hoon Yu, Sun Hee Kim, So Yeon Kim, Sung Hee Choi, Soo Lim, Yoon Seok Chang, Hak Jong Lee, Young Joo Park, Hak Chul Jang
Korean Diabetes Journal.2009; 33(1): 58. CrossRef

A Case of Hepatic Glycogenosis in a Patient with Uncontrolled Type 1 Diabetes Mellitus.: Seung Hwan Lee, Hyuk Sang Kwon, Jung Ah Shin, Won Chul Kim, Jeong Hoon Kim, Yoon Hee Choi, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2006;30(1):82-86. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.82

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Abstract PDF

When a patient with diabetes presents with hepatomegaly and increased level of liver enzymes, glycogenosis or nonalcoholic steatohepatitis (NASH) should be considered. Glycogenosis is mainly developed in patients with type 1 diabetes, when blood glucose level is poorly controlled, when a high dosage of insulin is administered in ketoacidosis, or when glucose is given to control hypoglycemia caused by high dosage of insulin. On the other hand, the main causes of NASH, which are known to mainly affect type 2 diabetes patients, are obesity, dyslipidemia or insulin resistance. Glycogenosis differs from NASH, the former being a reversible change that improves with the control of blood glucose level and the minimum dosage requirement of insulin, and the latter being a progressive disease that may lead to fibrosis or cirrhosis of the liver. However, clinical differentiation of the two diseases is difficult and liver biopsy is helpful for making a definite diagnosis. We present a type 1 diabetes patient with poorly controlled blood glucose level, who have had a frequent history of diabetic ketoacidosis, showing hepatomegaly and a slight increase in liver enzyme level. The patient was diagnosed as diabetic glycogenosis, confirmed by liver biopsy. Strict control of the blood glucose level resulted in rapid improvement showing the reversible nature of the disease.

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Four cases of type 1 diabetes mellitus showing sharp serum transaminase increases and hepatomegaly due to glycogenic hepatopathy
Yuichi Ikarashi, Tomomi Kogiso, Etsuko Hashimoto, Kuniko Yamamoto, Kazuhisa Kodama, Makiko Taniai, Nobuyuki Torii, Hiroko Takaike, Yasuko Uchigata, Katsutoshi Tokushige
Hepatology Research.2017;[Epub] CrossRef
Glycogenic hepatopathy in a Korean girl with poorly controlled type 1 diabetes mellitus
Hwal Rim Jeong, Young Seok Shim, Young Bae Kim, Hae Sang Lee, Jin Soon Hwang
Annals of Pediatric Endocrinology & Metabolism.2014; 19(1): 49. CrossRef
Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus
Jae Hwang Cha, Sang Ho Ra, Yu Mi Park, Yong Kwan Ji, Ji Hyun Lee, So Yeon Park, Soon Koo Baik, Sang Ok Kwon, Mee Yon Cho, Moon Young Kim
Clinical and Molecular Hepatology.2013; 19(4): 421. CrossRef
Hepatic glycogenosis in a patient with poorly controlled type 1 diabetes mellitus
Hye Young Jin, Dae-Young Kang, Jin-Ho Choi
Korean Journal of Pediatrics.2009; 52(11): 1279. CrossRef

The long-term effect of ramipril on Gialpha2-protein and Protein Tyrosine Phosphatase 1B in an animal model of type 2 diabetes(OLETF rat).: Jung Min Lee, Ok Ki Hong, Hyuk Sang Kwon, Sung Dae Moon, Sang Ah Chang, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Sung Koo Kang; Korean Diabetes J. 2006;30(1):25-38. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.25

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Abstract PDF: BACKGROUND
The regulation of tyrosine phosphorylation/dephosphorylation is an important mechanism in various intracellular metabolism. Also impaired insulin signal transduction is important in pathogenesis of type 2 diabetes. It has been reported that PTP1B is a negative regulator of insulin action, and Gialpha2-protein is related to the regulation of PTP1B. Herein we investigated the long-term effects of ramipril on PTP1B/insulin signal protein interaction and the relation between Gialpha2 and PTP1B in animal model of type 2 diabetes (OLETF rat). METHODS: OLETF rats and age-matched LETO rats were divided into two groups. One group of rats received ramipril (10 mg/kg body weight) for 12 weeks, and another group did not. Finally, each group was divided into 2 subgroups, with or without insulin injection intravenously, before sacrifice. After sacrifice, tissues extracts of liver, hind limb muscle, and epididymal fat were obtained for quantification of PTP1B, Gialpha2, and several insulin signal proteins by western blotting. RESULTS: In liver and muscle, the levels of basal PTP1B and activated PTP1B of OLETF rats treated with ramipril and insulin were significantly decreased. The levels of Gialpha2, activated IRS-2, and activated p-85alpha were significantly increased in OLETF rats treated with ramipril and insulin. In adipose tissue, the levels of Gialpha2 and activated p-85alpha of OLETF rats treated with ramipril and insulin were slightly increased as in liver and muscle. But, the levels of basal PTP1B and activated PTP1B were significantly increased. And, the levels of activated IRS-1 and activated IRS-2 were decreased. CONCLUSION: These results suggest that the improvement of insulin sensitivity by treatment with ramipril was related to the decreased level of activated PTP1B. Also, we could suggest that the changes of activated PTP1B level was related with the changes of Gialpha2-protein. However, the results of adipose tissue were different from those of liver and muscle. So it seemed likely that there would be various major modulators for regulation of insulin signal pathway according to tissue.

Induction of Immune Tolerance by Macrochimerism: Preliminary Study for Overcome of Islet Allograft Rejection.: Oak Kee Hong, Sung Joo Kim, Chung Gyu Park, Chul Woo Chung, Hyuk Sang Kwon, Yoon Hee Choi, Bong Yun Cha, Ho Yong Son, Kun Ho Yoon; Korean Diabetes J. 2005;29(2):112-121. Published online March 1, 2005

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Abstract PDF: BACKGROUND
Recently islet transplantation(TPx) has achieved remarkable results while it is not the ultimate solution yet because of a serious shortage of human pancreases, immune rejection and recurrence of autoimmunity. Immune tolerance induction is one of the ideal way for overcome the immune rejection and recurrence of autoimmunity after islet TPx. In this study, we tested the efficacy of the mixed chimerism conducted by minimally invasive regimens on induction of immune tolerance in allogenic skin transplantation model. METHODS: Busulfan(600microgram/mouse) was administered on day -1, and 0.1 mg monoclonal antibody against CD45RB and 0.5 mg monoclonal antibody against CD154 were administered intraperitoneally on days 0, 2, 4, and 6. We gave the C57BL/6 recipients either a standard-dose(2x107 bone marrow cells/mouse; SBMT-Ig) or a high-dose(20x107 bone marrow cells/mouse; HBMT-Ig) of bone marrow from BALB/c donors. After transplantation the, C57BL/ 6 recipients received BALB/c donor skin grafting on day 0. Untreated control animals in each group, both the SBMT and HBMT mice(without busulfan) were treated with marrow cells only, and they received transplanted skin grafts from the BALB/c donor on day 0. We monitored chimerism by flow cytometry and we monitored tolerance by skin grafting. RESULTS: Chimerism was significantly increased in all the groups and it peaked on day 56 after bone marrow transplantation. On day 56, chimerism in the peripheral blood did not significantly differ between the SBMT(15.0+/-3.6%) mice and the HBMT+Ig(15.3+/-6.5%) mice. Allogenic skin transplanted on the untreated mice was invariably lost within 20 days, with a mean survival time of 10.0+/-2.5 days for the SBMT mice and 13.3+/-4.9 days for HBMT mice. The skin survival rates were significantly greater for the SBMT+Ig mice(39.0+/-36.6days) and for the HBMT+Ig mice(79.9+/-43.6 days)(HBMT+Ig vs. SBMT P=0.006: HBMT+Ig vs. SBMT+Ig P=0.0087: HBMT+Ig vs. HBMT P=0.0093). Although three of the eight(37.5%) HBMT+Ig mice showed a high skin graft survival rate >120 days, the chimerism was 3.4+/-1.3% in the peripheral blood. In the HBMT+Ig mice, chimerism was higher in the thymus(8.05+/-9.7%) than in the peripheral blood and it was significantly higher than in the thymus of the HBMT mice(0.36+/-0.5%)(P< 0.05). CONCLUSIONS: These data shows that chimerism created by minimally invasive method with high-dose bone marrow and anti-CD45RB/CD154 antibody seems promissing way for prolongation of islet allograft survival

Effect of Captopril on Insulin Sensitivity for Subjects with Insulin Resistance.: Hye Jung Lee, Hyuk Sang Kwon, Jin Hee Lee, Sung Koo Kang, Yoon Hee Choi, Sung Ha Hwang, Seung Hyun Ko, Jung Min Lee, Kun Ho Yoon, Bong Yun Cha, Won Chul Lee, Kwang Woo Lee, Ho Young Son; Korean Diabetes J. 2004;28(5):416-424. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Angiotensin converting enzyme (ACE) inhibitors are becoming increasingly popular as the first-choice antihypertensive agents for diabetic patients. This could be partly related to their suggested beneficial effects on insulin sensitivity. This study was designed to compare the effect of captopril with that of control (nitrendipine) on insulin sensitivity for subjects with insulin resistance. METHODS: 24 subjects, aged less than 60 years, with their insulin resistance being defined as the area under the curve (AUCi) of insulin that was 2 standard deviations (SD) more than that of the control subjects during oral glucose tolerance test were recruited. A randomized, double-blind, crossover trial was conducted for an 8 weeks treatment period with captopril and the control (nitrendipine) that was given after an initial 6 weeks run-in period. Anthropometric measurement including weight, height, waist and hip circumference, blood pressure (systolic & diastolic), lipid profile blood chemistry, electrolytes levels & renal function testing, and frequently sampled intravenous glucose tolerance tests (FSIGT) for the insulin sensitivity index (SI) & acute insulin response to glucose (AIRg) were also done before and after treatment, respectively. RESULTS: 18 subjects (6 males, 12 females) completed the study. The mean age of the study subjects was 47.9+/-2.9 years (mean+/-SEM), and their BMI was 28.0+/-0.7 kg/m2 (mean+/-SEM).There was a significant decrease in weight (baseline; 71.5+/-9.2 kg vs. captopril; 70.7+/-9.0 kg and nitrendipine; 709+/-9.2 kg, p<0.05, respectively) and BMI (baseline; 28.0+/-3.0 kg/m2 vs. captopril; 27.7+/-2.8 kg/m2 and nitrendipine; 27.8+/-2.9 kg/m2, p<0.05, respectively) for both groups compared with the baseline, but there are no significant differences between the two groups. Triglyceride was significantly decreased after treatment with captopril compared to the baseline and nitrendipine (187.0+/-99.5 mg/dL vs. 224.5+/-134.2 mg/dL, respectively, p<0.05). The SI was significantly increased after captopril treatment compared with the baseline (1.4+/-1.0 vs. 2.5+/-0.8 min-1 per mU/ml, respectively, p<0.05), and the captopril group was significantly higher than that of nitrendipine (1.5+/-1.0 min-1 per mU/ml, p <0.05). Acute insulin response to glucose in both groups was also increased after treatment, but there was no statistically significance. CONCLUSION: Captopril therapy improved insulin sensitivity, and it decreased the concentration of fasting insulin in subjects with insulin resistance.

Relative Hyperglucagonemia and Its Related Factors in Patients with Type 2 Diabetes.: Kang Hyun Choi, Ki Ho Song, Sang Hoon Lee, Seong Hoon Chung, Eun Jung Kim, Seung Hyun Ko, Hyuk Sang Kwon, Yu Bae Ahn, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2004;28(4):338-345. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Excessive secretion of glucagon contributes to metabolic disturbance in type 2 diabetes. A hyperglucagonemic state is likely to be involved in increased hepatic glucose output resulting from both gluconeogenesis and glycogenolysis. The mechanism of hyperglucagonemia, though still unclear, is explained, in part, by the decreased sensitivity of cells to insulin or glucose and disturbances of the normal oscillatory secretory pattern of insulin. The aim of the study was to determine the extent of glucagon excess and its related factors in Korean patients with type 2 diabetes. METHODS: The subjects of this study were 21 controls and 102 type 2 diabetic patients. The blood glucose, glucagon and insulin concentrations were measured at 0, 30, 60, 90 and 120 min after ingestion of 75 g of glucose, and the areas under the curve (AUC) calculated. RESULTS: The AUC of plasma glucose (AUCgc) was significantly higher in the type 2 diabetic patients than in the controls (2,026.1585.8 vs. 854.8190.3 mmol/min, P<0.01), but there was no difference in the AUC of plasma glucagon (AUCgn) between the two groups. The AUCgn in the type 2 diabetic patients was positively correlated with the duration of diabetes (r=0.202, P<0.05) or HbA1c (r=0.208, P<0.05). The AUC of serum insulin (AUCin) was negatively correlated with the duration of diabetes (r=-0.291, P<001). AUCgn, AUCgc and HbA1c in long-term diabetic patients (duration of diabetes 10 years, n=32) were significantly higher compared with recently diagnosed patients (duration of diabetes <1 year, n=38) (11,362.35,981.9 vs. 9,097. 22,990.4 ng/min; 2,119.9519.0 vs. 1,832.2477.6 mmol/min; 9.52.0 vs. 8.32.1%, P<0.05). In addition, the AUCin and insulinogenic index in long-term patients were significantly lower compared with recently diagnosed patients. (Eds note: the highlighted figures are confusing, due to your various uses of commas and period marks, olease clarify?) CONCLUSIONS: Our results suggest that duration of diabetes and poor glycemic control might be closely associated with relative hyperglucagonemia in Korean type 2 diabetic paticnts.

Development of Adult Porcine Islet Isolation Method for Xenotransplantation.: Sung Rae Kim, Kun Ho Yoon, Hyuk Sang Kwon, Sun Hee Suh, Seung Hyun Ko, Jung Min Lee, Soon Jib Yoo, Yoo Bae Ahn, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2004;28(2):75-87. Published online April 1, 2004

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Abstract PDF: BACKGROUND
AND PURPOSE: Xenotransplantation using porcine islet cells might be an alternative to allotransplantation, which has been limited due to the lack of donors. Various researches using porcine islet cells have been performed in foreign countries; however, they have never been studies in Korea. Therefore, the purpose of this study was to explore the possibility of thise new treatment for cases of diabetes by establishing of improved islet isolation skill. METHODS: The pancreas and islets were extracted from pigs weighing around 100kg. To establish an islet isolation method, the islet yield, purity and the distribution size of the isolated islets were step wise compared in various ways, and then the superior method adopted. To determine the conveyance method after organ extraction, the conveyance method of pouring collagenase P was compared with the conveyance method of injecting Custidol. For digestion, the mechanical shaking and static incubation methods were also compared. To isolate islets from the digested pancreata, isolation methods were analyzed using 3 and 4 layers' Ficoll. The islet yield was appraised after their isolation using the optimized islet isolation method. To assess the results of the islet isolation, appraised the purity and the survival rates of cells, the insulin secretion resulting from the glucose stimulation test was examined. RESULTS: The method of injecting 4degrees C Custidol was effective for the conveyance and storage of the isolated pancreas in comparison with an injection of collagenase P(3465+/-1488 IEQ/g pancreas vs. 48+/-1.7 IEQ/g pancreas, p<0.01). The digestion method was superior to the mechanical shaking method at keeping a stable condition(3465+/-1488 IEQ/g pancreas vs. 1265+/-141.4 IEQ/g pancreas, p<0.01). Ficoll isolation using 3 layers gave the same results as using 4 layers. The average weights of the isolate Pancreatic islets was 23.8+/-3.3g. The numbers of islets per gram was 3465+/-1488.2(IEQ), with a the purity of 86.3+/-2.0%, and a survival rate of over 95%. The insulin secretion caused by glucose stimulation substantially increased in concentration from 24 to 72 hours(24hr: 5mM 3.12mU/mL --< 20mM 6.79mU/mL(2.17 fold), 72hr: 5mM 2.38mU/mL --< 9.93mU/mL(4.17fold))

Establishment of Blood Glucose Monitoring System using Internet.: Hee Soo Kim, Jae Hyoung Cho, Hyuk Sang Kwon, Jin Hee Lee, Bok Re Song, Jung A Oh, Kun Ho Yoon, Ho Young Son; Korean Diabetes J. 2003;27(3):280-287. Published online June 1, 2003

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Abstract PDF: BACKGROUND
The internet has been used world wide as a communication tool. To improve the quality of glucose control, the effectiveness of an Internet-based Blood Glucose Monitoring System (IBGMS), on changes in HbA1c levels, was investigated. RESEARCH DESIGN AND METHODS: A randomized clinical trial, involving 110 patients who had visited outpatient's clinic at the Kangnam St. Mary's Hospital diabetes center for 3 months, was conducted. The study subjects were treated with IBGMS for 12 weeks, with a control group receiving the usual outpatient management for the same period. HbA1C and other laboratory tests were performed at the baseline and at the end of the study. RESULTS: There were no significant differences found between the two groups at the baseline measurements, with respect to age, sex, diabetes duration, body mass index, blood pressure, HbA1C and other laboratory data. In the follow up tests, the study group showed a significant reduction in the HbA1C level, by 7.1% (0.54% absolute, p=0.001), while the control group showed an increased HbA1C level (p=0.054). Moreover, there was an 11.1% reduction (0.92% absolute, p<0.001) in the HbA1C level in the patients with HbA1C levels > or =7.0% at baseline in the study group, but those with HbA1C levels <7.0% maintained good HbA1c levels, 6.32%, by the end of the study. CONCLUSIONS: This new IBGMS resulted in a significant reduction in the HbA1C levels during the study period. We propose this IBGMS as a new method for glycemic control.

The Effects of High Glucose, Insulin and TGF-beta 1 on Proliferation and Differentiation of the Pancreatic Stellate Cells.: Oak Kee Hong, Hyuk Sang Kwon, Kyu Hyun Yeom, Marie Lee, Ji Hun Yang, Seung Hyeon Ko, Soon Jib Yoo, Hyun Sik Son, Kun Ho Yoon, Bong Yeon Cha, Kwang Woo Lee, Ho Yong Son, Sung Koo Kang; Korean Diabetes J. 2003;27(3):228-240. Published online June 1, 2003

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Abstract PDF: BACKGROUND
Although chronic pancreatitis gives rise to fibrosis of pancreatic exocrine tissue, and type 2 diabetes is accompanied by pancreatic fibrosis, the mechanisms of fibrogenesis in the pancreas have been insufficiently studied. The activated Pancreatic stellate cells (PSC) have recently been identified in human and experimental fibrotic areas from chronic panceatitis tissues. As PSC are similar in their morphology and biochemistry to hepatic stellate cells, they are suspected to play the same role in pancreatic fibrogenesis as the hepatic stellate cells in liver fibrosis. The PSC were isolated from the rat pancreata, and mediators stimulating the proliferation and differentiation identified. METHODS: The pancreatic stellate shaped cells were isolated by a minor modification to the method described by Apte et al (ref), using a Nycodenz gradient. The isolated PSCs were confirmed by phase-contrast and by the immunofluorescence of vimentin, desmin and smooth muscle a-actin (a-SMA). The level of alpha-SMA was quantified by Western blot in the PSCs in the culture, over time, and the cell proliferation was measured by 3[H]-Thymidine incorporation. The effect of the proliferation and differentiation of the PSC were assessed in relation to D-glucose (500 mg/dL), Insulin (10 IU/mL) and TGF-beta (10 ng/mL) treatment of the culture medium. RESULTS: The stellate shaped cells from the rat pancreata grew readily in the culture. Unactivated PSCs, cultured for 3 days, had an angular appearance, contained lipid droplets, manifesting positive vitamin A autofliuorescence, and stained positively for vimentin and desmin, but negatively for alpha-SMA. Within 4~8 days of primary culturing, the PSCs were activated, the sizes and numbers of the fat droplets decreased, the cells flattened, developed long cytoplasmic extensions and expressed alpha-SMA. After 3 passages, almost 100% of the cells were positive for alpha-SMA expression, indicating a myofibroblast type of differentiation in vitro. The addition of high-glucose concentrations and insulin to the activated PSCs significantly stimulated cell proliferation (194.4+/-8.3, 175.0+/-31.0 vs. control), and when the combination of high- glucose and insulin was applied, the cell proliferation was increased to an even greater extent (247.0+/-21.8 vs. control). CONCLUSIONS: Pancreata stellate cells can be isolated, and cultured in vitro, from normal SD rats. High concentrations of glucose and insulin in culture medium activated the PSC proliferation.

The Effect of Nitric Oxide on Insulin Binding and Insulin Receptor Recycling in Bovine Aortic Endothelial Cells.: Hyuk Sang Kwon, Oak Kee Hong, Hee Soo Kim, Jung Min Lee, Sung Rae Kim, Sung Dae Moon, Sang Ah Jang, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2003;27(3):213-227. Published online June 1, 2003

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Abstract PDF: BACKGROUND
The coexistence of insulin resistance and endothelial dysfunction is commonly observed in a variety of metabolic and cardiovascular disorders, including athero-sclerosis and type 2 diabetes mellitus. Because nitric oxide (NO), or nitric oxide synthase (NOS), has been suggested as a significant contributing factor in the development of endothelial dysfunction and insulin resistance, reactive NO or NOS were investigated to see if they contribute to the insulin internalization pathway. METHODS: The production of NO (Nitrite), the expression of eNOS (endothelial NOS), insulin binding and the insulin receptor internalization and recycling, following 48 hours of incubation with bradykinin (BK), acetylcholine (Ach), NG-monomethyl- L-arginine (L-NMMA) and N-nitro-L-arginine methylester (L-NAME) in Bovine aortic endothelial cells (BAECs), were examined. RESULTS: The results were as follows: 1. In relation to the time course, the production of eNOS was increased, but was decreased after 8 hours of incubation. The production of eNOS in the L-NMMA and L-NAME treated groups was significantly decreased compared with that of the controls (p<0.05). 2. The specific insulin bindings to the receptors of the endothelial cells were maximized within 20 mins, and then decreased. At 20 mins, the binding rate of the L-NMMA treated group was significantly decreased compared to that of the controls. At a concentration of 0.4ng/ml of unlabelled insulin, the specific insulin binding of the L-NMMA treated group was significantly decreased compared to that of the controls (p<0.05). 3. The internalization of 125I-insulin into the endothelial cells, as assessed by the acid washing dissociation method, occurred rapidly. The internalized radioactivity of 125I-insulin, at 20 mins, was significantly increased in the BK and Ach groups compared with the controls (p<0.05). 4. The recycling of the internalized insulin receptors showed no significant differences between the study groups, but the recycling was slightly delayed compared with controls in the Ach group. CONCLUSION: In conclusion, the NO generating substances, BK and Ach, and the inhibitory substance, L-NMMA, may influence the binding and internalization of insulin-insulin receptors. Our results suggest that NO might contribute to the transcytosis of insulin in BAECs

3-Dimensional Long Term Culture of Monolayer Cultured Dispersed Neonatal Porcine Pancreas Cells (NPCC).: Sun Hee Suh, Kun Ho Yoon, Hyuk Sang Kwon, Ok Ki Hong, Jung Min Lee, Ki Ho Song, Soon Jib Yoo, Hyun Sik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2002;26(5):383-395. Published online October 1, 2002

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Abstract PDF: BACKGROUND
We have reported porcine neonatal pancreas cell clusters (NPCCs) to be useful clinical alternative due to their growth potential and convenience. However, to apply the porcine NPCCs in human islet transplantation, there is a need to achieve in vitro maturation of porcine pancreas duct cells for the immediate cure of diabetes, and to escape hyperacute rejection. We have established a long-term 3D culture system of porcine pancreas duct cells for their in vitro induction in differentiated beta-cells. METHOD: For making NPCCs, pancreata from 1~3 days old pigs were minced, digested and cultured for 8 days. After 8 days, the cells were layered with Matrigel. After 50 days, the 3 dimensional cultures, the components of the reconstructed cell clusters were confirmed by three approaches: immunofluorescent staining, mea-surement of glucose stimulated insulin secretion and semiquantitative RT-PCR. RESULT: The monolayers of epithelial cells formed three-dimensional structures of cysts from which 50~200 micro meter diameter islet-like clusters of pancreas cells budded. The insulin and DNA contents, and the ratio of insulin/DNA, did not change significantly, even after 50 days of culturinge. The levels of insulin and galactosyl transferase mRNA showed a tendency to increase in the monolayer culture of the duct cells until day 8, after which the levels significantly decreased. However, the level of glucagon mRNA was maintained until day 50. Compared with their basal secretion at 5mM glucose, the cysts/cultivated porcine islet buds exposed to stimulatory 20mM glucose did not show difference in insulin secretion. CONCLUSION: We have shown the expansion of dispersed porcine neonatal pancreas cells in vitro, and the reconstruction of a three-dimensional structure, following Matrigel overlaying, but were unable to observe the transition of duct cells to beta cells, as observed in human duct cells. Further studies will be required to elucidate this difference.

The Role of Akt-1/PKBalpha on Insulin Action in 3T3-L1 Adipocyte.: Jung Min Lee, Hyun Shik Son, Hyuk Sang Kwon, Seung Ki Kwack, Seung Hyun Ko, Sang Ah Chang, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Prem Sharma; Korean Diabetes J. 2002;26(4):274-285. Published online August 1, 2002

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Abstract PDF: BACKGROUND
S: Akt/PKB as a serine/threonine kinase is stimulated by insulin and other growth factors. And insulin stimulates glucose uptake by promoting the translocation of glucose transporter 4 (GLUT4) to the cell membrane. But, it is not clear that Akt/PKB, a downstream target of PI 3-kinase, is involved in glucose uptake pathway. In this study, we investigated the role of Akt/PKB, especially Akt-1, on insulin action in 3T3-L1 adipocyte. METHODS: We made recombinant Ad5.Akt-1 vector by the insertion of Akt-1 gene to adenoviral vector. And then, we overexpressed Akt-1 proteins(wild type and kinase inactive type) in 3T3-L1 adipocytes by using a adenoviral transfection method. We observed the changes of glucose uptake, glycogen synthesis, activities of mitogen-activated protein kinase (MAPK, also called extracellular signal-regulated kinase), p70 ribosomal s6 protein kinase (p70s6k), and glycogen synthase kinase 3 (GSK3) according to Akt-1 activity and insulin treatment. RESULTS: First, overexpression of Akt-1 did not affect to glucose uptake, whether insulin stimulates or not. Second, overexpression of Akt-1 did not affect the phosphorylation of p44/42-MAPK, either. Third, the glycogen synthesis was increased by overexpression of Akt-1. CONCLUSION: Akt-1 activation is necessary for glycogen synthesis, but is not essential for glucose transport in 3T3-L1 adipocytes.

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