- Effects of Anti-Vascular Endothelial Growth Factor (VEGF) on Pancreatic Islets in Mouse Model of Type 2 Diabetes Mellitus.
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Ji Won Kim, Dong Sik Ham, Heon Seok Park, Yu Bai Ahn, Ki Ho Song, Kun Ho Yoon, Ki Dong Yoo, Myung Jun Kim, In Kyung Jeong, Seung Hyun Ko
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Korean Diabetes J. 2009;33(3):185-197. Published online June 1, 2009
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DOI: https://doi.org/10.4093/kdj.2009.33.3.185
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Abstract
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- BACKGROUND
Vascular endothelial growth factor (VEGF) is associated with the development of diabetic complications. However, it is unknown whether systemic VEGF treatment has any effects on the pancreatic islets in an animal model of type 2 diabetes mellitus. METHODS: Anti-VEGF peptide (synthetic ATWLPPR, VEGF receptor type 2 antagonist) was injected into db/db mice for 12 weeks. We analyzed pancreatic islet morphology and quantified beta-cell mass. Endothelial cell proliferation and the severity of islet fibrosis were also measured. VEGF expression in isolated islets was determined using Western blot analysis. RESULTS: When anti-VEGF was administered, db/db mice exhibited more severe hyperglycemia and associated delayed weight gain than non-treated db/db mice. Pancreas weight and pancreatic beta-cell mass were also significantly decreased in the anti-VEGF-treated group. VEGF and VEGF receptor proteins (types 1 and 2) were expressed in the pancreatic islets, and their expression was significantly increased in the db/db group compared with the db/dm group. However, the elevated VEGF expression was significantly reduced by anti-VEGF treatment compared with the db/db group. The anti-VEGF-treated group had more prominent islet fibrosis and islet destruction than db/db mice. Intra-islet endothelial cell proliferation was also remarkably reduced by the anti-VEGF peptide. CONCLUSION: Inhibition of VEGF action by the VEGF receptor 2 antagonist not only suppressed the proliferation of intra-islet endothelial cells but also accelerated pancreatic islet destruction and aggravated hyperglycemia in a type 2 diabetes mouse model. Therefore, the potential effects of anti-VEGF treatment on pancreatic beta cell damage should be considered.
- A Nationwide Survey about the Current Status of Glycemic Control and Complications in Diabetic Patients in 2006: The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus.
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Soo Lim, Dae Jung Kim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee
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Korean Diabetes J. 2009;33(1):48-57. Published online February 1, 2009
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DOI: https://doi.org/10.4093/kdj.2009.33.1.48
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3,225
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Abstract
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- BACKGROUND
The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus performed a nationwide survey about the current status of glycemic control and diabetic complications in 2006. METHODS: The current study included 5,652 diabetic patients recruited from the rosters of endocrinology clinics of 13 tertiary hospitals in Korea. Age, gender, height, weight, waist circumference and blood pressure were investigated by standard method. Fasting and postprandial 2 hour glucose, glycosylated hemoglobin (HbA1c), lipid profiles, fasting insulin and c-peptide levels were measured. Microvascular (microalbuminuria, retinopathy and neuropathy) and macrovascular (coronary artery disease [CAD], cerebrovascular disease [CVD] and peripheral artery disease [PAD]) complications were reviewed in their medical records. RESULTS: Mean age of total subjects was 58.7 (+/- 11.6) years and duration of diabetes was 8.8 (0~50) years. Mean fasting and postprandial 2 hour glucose levels were 145.9 +/- 55.0 and 208.0 +/- 84.4 mg/dL, respectively. Their mean HbA1c was 7.9 +/- 1.9%: the percentage of patients within target goal of glycemic control (< 7% of HbA1c) was 36.7%. In this study, 30.3%, 38.3% and 44.6% of patients was found to have microalbuminuria, retinopathy and nephropathy, respectively. Prevalence of CAD, CVD and PAD was 8.7%, 6.7% and 3.0%, respectively. Diabetic complications were closely related with age, duration of diabetes and glycemic control, and this relationship was stronger in microvascular complications than macrovascular ones. CONCLUSION: Only about one third of patients with diabetes was found to reach target glycemic control in tertiary hospitals of Korea. More tight control is needed to reduce deleterious complications of diabetes in Korea.
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Jin Hwa Kim The Journal of Korean Diabetes.2013; 14(1): 11. CrossRef - The Relationship between Neuropathic Pain and Glycemic Control, Self Management in Type II Diabetes Mellitus Patients
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Hye Soon Kim, A Mi Shin, Mi Kyung Kim, Yoon Nyun Kim The Korean Journal of Internal Medicine.2012; 27(2): 197. CrossRef - Low ankle-brachial index is an independent predictor of poor functional outcome in acute cerebral infarction
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Sun-Joo Boo Korean Journal of Adult Nursing.2012; 24(4): 406. CrossRef - Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus in Korea
Seung-Hyun Ko, Bong-Yun Cha Diabetes & Metabolism Journal.2012; 36(1): 6. CrossRef - The Association of Self-Reported Coronary Heart Disease with Diabetes Duration in Korea
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Ji Hee Yu, Ki-Up Lee Diabetes & Metabolism Journal.2012; 36(1): 77. CrossRef - Reduction in glycated albumin can predict change in HbA1c: comparison of oral hypoglycaemic agent and insulin treatments
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Alireza Didarloo, Davoud Shojaeizadeh, Hassan Eftekhar Ardebili, Shamsaddin Niknami, Ebrahim Hajizadeh, Mohammad Alizadeh Diabetes & Metabolism Journal.2011; 35(5): 513. CrossRef - Factors that Affect Medication Adherence in Elderly Patients with Diabetes Mellitus
Kyung-Ae Park, Jung-Guk Kim, Bo-Wan Kim, Sin Kam, Keon-Yeop Kim, Sung-Woo Ha, Sung-Taek Hyun Korean Diabetes Journal.2010; 34(1): 55. CrossRef - The Effects of Tailored Diabetes Education on Blood Glucose Control and Self-Care
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- Prevalence of the Metabolic Syndrome in Type 2 Diabetic Patients.
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Tae Ho Kim, Dae Jung Kim, Soo Lim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee
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Korean Diabetes J. 2009;33(1):40-47. Published online February 1, 2009
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DOI: https://doi.org/10.4093/kdj.2009.33.1.40
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2,791
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Abstract
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- BACKGROUND
The aim of this study was to analyze the prevalence of metabolic syndrome in Korean type 2 diabetic patients. METHODS: A total of 4,240 diabetic patients (male 2,033, female 2,207; mean age 58.7 +/- 11.3 years; DM duration 8.9 +/- 7.6 years) were selected from the data of endocrine clinics of 13 university hospitals in 2006. Metabolic syndrome was defined using the criteria of the American Heart Association/National Heart Lung and Blood Institute and the criteria of waist circumference from the Korean Society for the Study of Obesity. RESULTS: The prevalence of metabolic syndrome was 77.9% (76.7% of males, 78.9% of females). The average number of the components of metabolic syndrome was 2.4 +/- 1.1. Abdominal obesity was seen in 56.8% of the patients, hypertriglyceridemia in 42.0%, low HDL cholesterol in 65.1%, and high blood pressure in 74.9%. Abdominal obesity and high blood pressure were much more prevalent among females than males, and low HDL cholesterol was much more prevalent among males than females. The prevalence of metabolic syndrome was not different according to the duration of diabetes. Metabolic syndrome was strongly related with obesity (odds ratio, 6.3) and increased age (odds ratio in the over 70 group, 3.4). CONCLUSION: The prevalence of metabolic syndrome was 77.9% in Korean type 2 diabetic patients. Its prevalence was greater in obese patients and in those over 40 years of age.
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Citations
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- Metabolic syndrome among patients with type 2 diabetes in Jordan: A cross-sectional study
Dana Hyassat, Ala’a Al-Refai, Yousef S. Khader, Malik E. Juweid, Saja AlSharaydeh, Nadera Layyous, Husam Aljabiry, Ahmad AlDurgham, Laith Z. Baqain, Joud Abu Summaqa, Rana Al-Shimi, Fatima Mohammad Atieh, Awn Mahasneh, Shaker Alaraj, Alanoud Al-wakfi, Oma Medicine.2024; 103(46): e40602. CrossRef - A Novel Clinical Predictor of Metabolic Syndrome: Vascular Risk Age
Abdulrahman Naser, Didar Elif Akgün, Rengin Çetin Güvenç, Samet Sayılan, Özgen Şafak Bagcilar Medical Bulletin.2023; 9(1): 1. CrossRef - Risk of Carotid Atherosclerosis in Subjects with Prediabetes Overlapping Metabolic Syndrome
Seol A Jang, Kyoung Min Kim, Seok Won Park, Chul Sik Kim Metabolic Syndrome and Related Disorders.2022; 20(10): 599. CrossRef - Metabolic Age, an Index Based on Basal Metabolic Rate, Can Predict Individuals That are High Risk of Developing Metabolic Syndrome
Sarahi Vásquez-Alvarez, Sergio K. Bustamante-Villagomez, Gabriela Vazquez-Marroquin, Leonardo M. Porchia, Ricardo Pérez-Fuentes, Enrique Torres-Rasgado, Oscar Herrera-Fomperosa, Ivette Montes-Arana, M. Elba Gonzalez-Mejia High Blood Pressure & Cardiovascular Prevention.2021; 28(3): 263. CrossRef - Metabolic syndrome among type 2 diabetic patients in Sub-Saharan African countries: A systematic review and meta-analysis
Wondimeneh Shibabaw Shiferaw, Tadesse Yirga Akalu, Mihretie Gedefaw, Denis Anthony, Ayelign Mengesha Kassie, Worku Misganaw Kebede, Henok Mulugeta, Getenet Dessie, Yared Asmare Aynalem Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2020; 14(5): 1403. CrossRef - Optimal Waist Circumference Cutoff Value Based on Insulin Resistance and Visceral Obesity in Koreans with Type 2 Diabetes
Jung Soo Lim, Young Ju Choi, Soo-Kyung Kim, Byoung Wook Huh, Eun Jig Lee, Kap Bum Huh Diabetes & Metabolism Journal.2015; 39(3): 253. CrossRef - The Relations between Diabetic Dietary Compliance, Dietary Intake, and Physical Activity and the Prevalence of Metabolic Syndrome (MS) in Type 2 Diabetic Patients
Dong Eun Kim, Seung Hee Hong, Ji-Myung Kim Korean Journal of Community Nutrition.2015; 20(5): 351. CrossRef - The Comparison between Periodontal Health Status and the Findings of Hypertension and Diabetes Disease of some Workers
In-Young Ku, Seon-Jeong Moon, Kyung-Hwan Ka, Myeong-Seon Lee The Korean Journal of Health Service Management.2013; 7(2): 81. CrossRef - The Relationship between Factors of Metabolic Syndrome in Korean Adult Males and the Parents' Family History of Diabetes
Hyung-Su Park, Jin-Gyu Jeong, Jin-Ho Yu The Journal of the Korea institute of electronic communication sciences.2013; 8(5): 779. CrossRef - Associations of serum fetuin-A levels with insulin resistance and vascular complications in patients with type 2 diabetes
Chan-Hee Jung, Bo-Yeon Kim, Chul-Hee Kim, Sung-Koo Kang, Sang-Hee Jung, Ji-Oh Mok Diabetes and Vascular Disease Research.2013; 10(5): 459. CrossRef - Cardio-Metabolic Features of Type 2 Diabetes Subjects Discordant in the Diagnosis of Metabolic Syndrome
Sa Rah Lee, Ying Han, Ja Won Kim, Ja Young Park, Ji Min Kim, Sunghwan Suh, Mi-Kyoung Park, Hye-Jeong Lee, Duk Kyu Kim Diabetes & Metabolism Journal.2012; 36(5): 357. CrossRef - Comorbidity Study on Type 2 Diabetes Mellitus Using Data Mining
Hye Soon Kim, A Mi Shin, Mi Kyung Kim, Yoon Nyun Kim The Korean Journal of Internal Medicine.2012; 27(2): 197. CrossRef - Therapeutic Target Achievement in Type 2 Diabetic Patients after Hyperglycemia, Hypertension, Dyslipidemia Management
Ah Young Kang, Su Kyung Park, So Young Park, Hye Jeong Lee, Ying Han, Sa Ra Lee, Sung Hwan Suh, Duk Kyu Kim, Mi Kyoung Park Diabetes & Metabolism Journal.2011; 35(3): 264. CrossRef - The Correlations between Extremity Circumferences with Total and Regional Amounts of Skeletal Muscle and Muscle Strength in Obese Women with Type 2 Diabetes
Hwi Ryun Kwon, Kyung Ah Han, Hee Jung Ahn, Jae Hyuk Lee, Gang Seo Park, Kyung Wan Min Diabetes & Metabolism Journal.2011; 35(4): 374. CrossRef
- Clinical Characteristics and Analysis of Risk Factor for Gastroesophageal Reflux Disease in Diabetic Patient.
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Kwang Hyuk Park, Seong Bo Yoon, Min Ho Jo, Eon Kyung Hong, Seong Jin Lee, In Kyung Jeong, Chul Young Park, Ki Won Oh, Hyun Kyu Kim, Jac Myoung Yu, Doo Man Kim, Sung Hee Lim, Moon Ki Choi, Hyung Jun Yoo, Sung Woo Park, Heung Young Oh, Jin Bae Kim, Il Hyun Baek, Myung Seok Lee
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Korean Diabetes J. 2005;29(4):358-366. Published online July 1, 2005
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Abstract
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- BACKGROUND
A high prevalence of gastroesophageal reflux disease(GERD) has been reported in diabetic patient. However, the exact mechanisms of GERD in diabetic patient have not been described. In several studies, diabetic neuropathy and dysfunction of the autonomic nervous system have been suggested as risk factors of GERD. However, there have been no studies on the exact prevalence or risk factors of GERD in Korean diabetic patients. Therefore, the prevalence of GERD in Korean diabetics patients was examined, and the risk factors for GERD, the differences in symptoms between GERD and non-GERD patients, and the degree of symptom relief after treatment were also analyzed. METHODS: A total of 310 diabetic patients, who underwent an upper gastroendoscopy due to diverse gastrointestinal symptoms, between April 2001 and November 2003, were enrolled. The diagnostic criteria or GERD included the upper gastroendoscopic view, which was analyzed using the scale of 'The Los Angeles Classification of Esophagus' from grades A to D. The prevalence and symptoms of GERD patients and the variable risk factors, such as blood glucose level, smoking and diabetic neuropathy, were examined. RESULTS: 1) There was an 18.4% prevalence of GERD in diabetic patients. 2) The clinical characteristics, including sex, age and serum lipid level, of the GERD group were not significantly different to those of the control group. However, the duration of smoking, the fasting and postprandial 2-hour serum glucose levels, and the diabetic neuropathy significantly affected GERD, 3) The main symptoms of the GERD group were dyspepsia(47.4%) and heart burn(26.3%). 4) The degree of subjective symptom relief in the GERD group after treatment with the proton pump inhibitor, pantoprazole(40mg), was remarkably lower than in the control group for approximately 1 month. CONCLUSION: In this study, the prevalence of GERD in diabetic patient was higher than that found in the general population which suggests that GERD in diabetic patient was due to a poorly controlled serum glucose level and diabetic neuropathy. The chief complaints pertaining to gastrointestinal symptoms in both study groups were non-specific. However, the recovery from symptoms in the GERD group was lower than the control group following drug therapy. The causes of the lower response rate in the GERD group will need to be examined in further studies.
- The Role of cAMP/PKA Activation on Exendin-4-Induced Cyclin D1 Expression in INS-1 Cell.
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Gyeong Ryul Ryu, Jung Hoon Kang, Hwa In Jang, Seung Hyun Ko, In Kyung Jeong, Duck Joo Rhie, Shin Hee Yoon, Sang June Hahn, Yang Hyeok Jo, Myung Suk Kim, Myung Jun Kim
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Korean Diabetes J. 2005;29(4):295-303. Published online July 1, 2005
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Abstract
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- BACKGROUND
Glucagon-like peptide-1(GLP-1) and exendin-4(EX-4) have been known to induce pancreatic islet proliferation and increases in the betacell mass. Cyclin D1 is a key protein responsible for the entry of the G into the S phase, thereby contributing to cell proliferation. Therefore, the effect of EX-4 on the expression of cyclin D1 in INS-1 cells, a rat pancreatic betacell line, was investigated. The involvement of either mitogen-activated protein kinases(MAPKs) or cyclic adenosine 5'-monophosphate/protein kinase A(cAMP/ PKA) in the EX-4-induced cyclin D1 expression was also examined. METHODS: INS-1 cells were treated with EX-4 (10 nM), and the cyclin D1 protein levels then determined by Western blot. To investigate the involvement of MAPKs in the EX-4- induced cyclin D1 expression, either a combined treatment of MAPKs inhibitors or transient transfection of extracellular signal-regulated kinase-1 (ERK1) was performed. The effect of cAMP on the EX-4-induced cyclin D1 expression was also examined by treatments with forskolin, an adenylyl cyclase activator, and H-89, a PKA inhibitor. RESULTS: EX-4 increased the expression of cyclin D1 protein in a dose-dependent manner. Although EX-4 induced phosphorylation of ERK1/2, the treatment with PD 98059 or the overexpression of ERK1 had no effect on the EX-4-induced cyclin D1 expression. However, forskolin significantly induced the expression of cyclin D1, whereas the pretreatment of H-89 inhibited the EX-4-induced cyclin D1 expression. CONCLUSION: These results suggest that EX-4 induce cyclin D1 expression in INS-1 cells via cAMP/PKA pathway, but this is not due to ERK activation.
- Mitogenic Effects and Signaling Pathway of Insulin-Like Growth Factor-I (IGF-I) in the Rat Beta Cell Line (INS-1).
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In Kyung Jeong, Ja Young Kim, Hyung Joon Yoo, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2004;28(6):478-489. Published online December 1, 2004
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Abstract
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- BACKGROUND
Nutrients and growth factors are known to stimulate pancreatic beta cell mitogenesis. IGF-I acts as a survival factor by limiting apoptosis and stimulating proliferation in many cell types. However, the appropriate mitogenic signaling pathways have not been defined. The aim of this study is to elucidate the mitogenic effect and signaling pathways of IGF-I in the rat beta cell line (INS-I). METHODS: The studies were performed using the rat pancreatic beta cell line, INS-1. INS-1 cells were cultured in RPMI 1640 containing serum-free, 0.2% BSA and 11.1 mmol/L glucose media for 24 hours, and the cells were then treated with IGF-I and different concentrations of glucose or tyrosine phosphorylation inhibitors, or insulin. The cell proliferation was measured by the [3H]thymidine uptake and MTT assay. The cell cycle was analyzed by a flow cytometer by using propidium iodide staining. Western blot analyses were performed using antibodies against PY20 and phospho-MAPK. RESULTS: 1) MTT assay and the [3H]thymidine uptake showed that IGF-I stimulated the INS-1 cell proliferation in a dose dependent manner. Glucose was noted to independently increase the INS-1 cell proliferation. A combination of IGF-I and glucose has a synergistic effect on the proliferation of INS-I cells. Insulin did not influence on the mitogenic effect of IGF-I. 2) The S fraction of INS-1 cells treated with IGF-I was increased in a dose dependent manner. IGF-I stimulated the exit from G1 into the S phase of the cell cycle. 3) Investigation of the role of the PI3K and MAPK, by using of the inhibitors LY294002, wortmannin, and PD98059, demonstrated that the activation of MAPK, but not PI3K, required to stimulate the proliferation of INS-1 cells. 4) IGF-I stimulated the phosphorylation activation of pp60 and phospho-MAPK in the INS-1 cells. IGF-I induced the beta cell proliferation, and this was mediated via a signaling mechanism that was facilitated by MAPK. CONCLUSION: The proliferative effect of IGF-I on pancreatic beta cell seems to be mediated through MAPK signaling pathway.
- The Influence of Metabolic Syndrome on the Intima-Medial Thickness and Cardiovascular Risk Factors in Type 2 Diabetes.
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Kwang Pyo Son, Young Je Chae, Tae Yu Lee, In Kyung Jeong, Mina Hur, Gu Young Jo, Young Lee, Seong Jin Lee, Chul Young Park, Ki Won Oh, Eon Kyung Hong, Hyun Kyu Kim, Jae Myoung Yu, Doo Man Kim, Sung Hee Lim, Moon Ki Choi, Hyung Jun Yoo, Sung Woo Park
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Korean Diabetes J. 2004;28(5):392-406. Published online October 1, 2004
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- BACKGROUND
Metabolic syndrome (MS) is usually present in type 2 DM (T2DM), and it is associated with atherosclerosis. The aim of this study is to exam the influence of MS on the intima-medial thickness(IMT) and the cardiovascular risk factors for type 2 diabetic patients. SUBJECTS AND METHODS: A cross sectional study was performed on 82 patients with Type 2 diabetes mellitus (DM) and 84 healthy controls. MS was defined according to the NCEP-ATP III criteria. Those subjects with any history of cerebro vascular accident, ischemic heart disease or acute inflammation were excluded. The cardiovascular risk factors (hsCRP, lipid profile, homocysteine, and uric acid), the status of glucose metabolism (HbA1c, fasting glucose, insulin, and HOMA-IR), the diabetic microvascular complications and the IMT at both common carotid arteries were measured. RESULTS: 1) For patients with T2DM, the levels of waist circumference, blood pressure, TG (1.7+/-1.4 vs 2.2+/-1.4 mmol/L), HDL-C (1.5+/-0.4 vs. 1.3+/-0.3 mmol/L), LDL-C (2.7+/-0.7 vs 3.1+/-0.9 mmol/L), TC/HDL-C (3.5 vs. 41), log of (hsCRP) (-0.11+/-0.4 vs 0.17+/-0.4), mean carotid IMT (0.63+/-0.12 vs. 0.74+/-0.12 mm) and max IMT (0.68+/-0.14 vs. 0.86+/-0.15 mm) were significantly different from the healthy control group. 2) The prevalence of MS in the T2DM groups was 64%. However, a decrease of the waist circumference, as measured by the modified Asian criteria, increased the crude prevalence of MS by up to 75%. 3) Diabetic patients with MS had a higher incidence of hypertension, a lower level of HDL-C, and higher levels of waist circumference, HOMA-IR, TG, and TC/HDL-C, a greater extent of microvasculopathy, an increased log (hsCRP), homocysteine, and carotid IMT than did diabetic patients without MS. 4) Among the component of MS, the presence of hypertriglyceridemia had an influence on the IMT mean and max. 5) The carotid IMT of patients with DM correlated with age, homocysteine, log (hsCRP), and uric acid on univariate analysis, and age and homocysteine we found to be independent risk factors of carotid IMT on multivariated analysis. CONCLUSION: Metabolic syndrome in subjects with glucose intolerance increases the risk of atherosclerosis.
- Activin A Converts Pancreatic Ductal Cells into Insulin-Secreting Cells.
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Kyoung Hee Lee, Mi Kyung Park, Han Wook Kang, Hyun Jin Kim, In Kyung Jeong, Hyung Joon Yoo, Jae Hoon Jeong, Yong Ki Min, Myung Shik Lee, Kwang Won Kim, Moon Kyu Lee
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Korean Diabetes J. 2004;28(1):20-27. Published online February 1, 2004
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Abstract
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Islet transplantation as a potential treatment for diabetes has been investigated extensively over the past years. One of the major limitations to successful islet transplantation is shortage of insulin-producing tissue, which has stimulated the search for alternative sources, and recently, attention has been focused on the possible use of controlled differentiation of stem cells to obtain specialized cells useful in treating many diseases. It is currently believed that pancreatic progenitor or stem cells exist in the ductal cell population. Activin A is a member of the TGFbeta superfamily, which can block the exocrine pancreatic development and potentiate the endocrine development of the pancreas. In this study, whether activin A could expand and/or differentiate the ductal cells into insulin-producing cells was examined. METHODS: From a collagenase P digested pancreas, ductal tissue was cultured under conditions that allowed expansion as a monolayer, where the cells were overlaid with a rat tail collagen I-coated dish. Activin A cDNA was transfected into rat ductal cells by using Lipofectamine, and the insulin secretion, content and differentiation markers examined. RESULT: The clumps of ductal tissue adhered to the dish 24 hr later, and formed a complete monolayer after 3 days of culture. Activin A overexpression significantly increased both the insulin secretion and content from the ductal cells. The glucose(16.7mM)-induced insulin secretion was also significantly increased. Immunohistochemistry and RT-PCR analyses revealed expression of PDX-1, as well as insulin & GLUT2. CONCLUSION: Activin A overexpression could potentiate the differentiation of pancreatic ductal cells, which might provide a potential new source of cinsulin- producing cells for transplantation
- Effect of Glucose Concentrations on the Cell Proliferation and Expression of L-type Calcium Channel mRNA in Cultured Rat Aortic Vascular Smooth Muscle Cells.
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Young Jung Cho, Hyung Joon Yoo, Hong Woo Nam, Ji Young Suh, In Kyung Jeong, Sung Hee Ihm, Hyeon Kyu Kim, Cheol Young Park, Jae Myung Yoo, Doo Man Kim, Moon Gi Choi, Sung Woo Park
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Korean Diabetes J. 2003;27(3):253-259. Published online June 1, 2003
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Abstract
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Vascular smooth muscle cell (VSMC) proliferation is one of the major pathogenic mechanisms for atherosclerosis. It is known that L-type calcium channels play a role in VSMC proliferation in diabetic rats. However, there have been no studies that show an association between the L-type calcium channels and the VSMC proliferation due to various glucose concentrations in the culture media. Therefore, the association between the voltage-dependent L-type calcium channels of the VSMCs, and the growth of vascular smooth muscle cells, was examined. METHODS: Rat aortic VSMCs were isolated from the aorta of Sprague-Dawley and OLETF rats, using an enzymic method. The VSMCs were cultured in various concentrations of glucose (5.5, 11.0, 16.6, 25, 30 and 40 mM). The VSMCs (1x10(4) cells in 24-well plates) were incubated in the presence of Bay K 8644 (10(-6)M), both with and without verapamil (10(-6)M), for 48 hours. The proliferation was then assessed by the MTT (methylthiazole tetrazolium) assay, and the expression of L-type calcium channel mRNA by RT-PCR. RESULTS: The vascular smooth muscle cell proliferation was significantly increased, in a dose-dependent manner, with glucose concentrations below 25 mM in both in a dose-dependent manner, with glucose concentrations below 25 mM in both kinds of rat. However, the increase in the VSMC proliferation of the OLETF rat was significantly higher than in the Sprague-Dawley rat. After the Bay K 8644 treatment, with the same glucose concentration, the VSMC proliferation and the expression of L-type calcium channel mRNA were significantly increased in both kinds of rat. After treatment with verapamil, the increased VSMC proliferation and expression of L-type calcium channel mRNA, due to the Bay K 8644, were suppressed to control levels in both kinds of rat. CONCLUSION: The results suggest that below certain concentrations of glucose, 25 mM, the L-type calcium channels may play a role in the VSMC proliferation of OLETF and Sprague-Dawley rats. The growth of the VSMCs in OLETF rats, due to various glucose concentrations (< 25 mM), was significantly higher than in the Sprague-Dawley rats.
- Effects of Peroxisome Proliferator-activated Receptor-gamma(PPARgamma) on the Pancreatic beta Cell Proliferation.
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Jung Hyun Noh, Tae Young Yang, In Kyung Jeong, Jae Hun Chung, Yong Ki Min, Myung Shik Lee, Kwang Won Kim, Moon Kyu Lee
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Korean Diabetes J. 2003;27(3):241-252. Published online June 1, 2003
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The effects and mechanisms of PPARgamma ligands on the cell proliferation in pancreatic beta cells were examined. METHODS: PPARgamma 1 cDNA was overexpressed in INS-1 cells using an adenoviral vector. The cell proliferations were measured by the MTT assay method, following the treatments with troglitazone (TGZ), rosiglitazone (RGZ), 15d-prostaglandin J2 (15d-PGJ2) or retinoic acid (RA), at increasing doses, in INS-1 and PPARgamma overexpressed INS-1 cells. The apoptosis, telomere length and cell cycles were determined after the PPARgamma ligand treatment. RESULTS: The long-term incubation, with PPARgamma ligands over 24 hr, inhibited the INS-1 cell proliferation rate. Apoptosis was not observed with the PPARgamma ligand treatment. G1 cell cycle arrest was observed with the troglitazone treatment. The telomere length remained unchanged following the TGZ treatment. The basal cell proliferation rate was unaffected by the overexpression of PPARgamma . After 48 h of TGZ treatment, the proliferation of the INS-1 cells was inhibited, in a dose- dependent manner, both with and without the overexpression. Moreover, the degree of inhibition was exaggerated in the PPARgamma overexpressed cells compared to beta gal overexpressed cells. CONCLUSION: PPARgamma ligands have direct inhibitory effects on the proliferation of INS-1 cells. Although the basal cell proliferation rate was not affected by PPARgamma overexpression, the PPARgamma overexpression and PPARgamma ligands have a synergistic inhibitory effect on the cell proliferation rate in pancreatic beta cells. G1 cell cycle arrest may be involved in the reduction of cell proliferation due to PPARgamma ligands.
- Comparative Study about the Effects of Acarbose and Voglibose in Type 2 Diabetic Patients.
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In Kyung Jeong, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Yun Ey Chung, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 2002;26(2):134-145. Published online April 1, 2002
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Abstract
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Acarbose and voglibose are alpha-glucosidase inhibitors. Although different pharmacological effects and adverse abdominal events associated with the two drugs have been reported, no study directly compared acarbose and voglibose in diabetes has been undertaken. To compare the pharmacological effects and gastrointestinal adverse events between two drugs, a randomized, placebo-controlled, double-blind study was performed in type 2 diabetes patients. METHODS: The period of study was 12 weeks (observation period: 4 weeks; treatment period: 8 weeks). Fifty-three patients were randomized into two groups (the acarbose group: 24 patients; the voglibose group: 29 patients). The serum glucose, insulin, fructosamine, HbA1c, cholesterol, triglyceride and the incidence of adverse events were measured. RESULTS: 1) The reduction of glucose from before treatment to 4 weeks after treatment was significantly higher in the acarbose group, but the change before treatment and 8 weeks after treatment in the two groups was similar (p = 0.569). 2) The insulin significantly decreased after voglibose treatment (p = 0.040). 3) HbA1c level tended to decrease in voglibose group, and there was a significant decrease after acarbose treatment. However, the change in HbA1c level before and after treatment was similar between the two groups (p = 0.412). 4) The two drugs did not cause any other changes in the total, HDL-cholesterol and triglyceride. 5) The number of patients with gastrointestinal adverse events was significantly low 4 weeks after voglibose treatment (p = 0.049), but the incidence in the two groups was similar after 8 weeks (p = 0.215). CONCLUSIONS: Acarbose and voglibose significantly improved postprandial hyperglycemia in diabetes. The incidence of gastrointestinal adverse events was low 4 weeks after voglibose treatment.
- The Effect of Step-wised, Controlled Cooling Method for Islet Cryopreservation on the in vivo and in vitro Islet Function.
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In Kyung Jeong, Seung Hoon Oh, Byung Joon Kim, Tae Young Yang, Byung Wan Lee, Chang Young Ha, Jung Hyung Noh, Jae Hoon Chung, Young Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2002;26(1):65-74. Published online February 1, 2002
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Abstract
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Although islet transplantation has been attempted to reverse the state of diabetes, achieving a critical number of islets and modulating the immune response limit the success ofl islet transplantation. Cryo-preservation of islets offers many important benefits for islet transplantation by collecting islets with a wide variety of HLA phenotypes and islet MHC expression. The aims of this study was to determine the optimal conditions for cryo-preservation by using a controlled cooling method and to evaluate in vitro and in vivo functional properties of the cryo-preserved islets. METHODS: Collagenase-isolated, Ficoll-purified islets were cultured for 48 hours. They were aliquoted into freezing tubes (1000 islets per tube), equilibrated with 2 M dimethyl sulfoxide (DMSO) in three steps, supercooled, nucleated, and controll- cooled at rate of 0.25 degrees C/min to - 40 degrees C prior to storage at - 196 degrees C. Rapid thawing and removal of DMSO with 0.75 M sucrose preceded 48 hour of culture and the morphology, viability, glucose-induced insulin secretion, and in vivo function of rats transplanted with cryopreserved islets was reexamined. RESULTS: 1) Recovery was 90.2+/-0.2%, 85.7+/-0.1% and 81.7+/-0.1% immediately after, 24 hours and 72 hours after thawing respectively. The viability was 60+/-5%, 80+/-5%, 90+/-5% immediately after, 24 hours and 72 hours after thawing respectively. 2) The glucose-stimulated-insulin secretion (GSIS) tended to decrease immediately after thawing, but GSIS increased to the level of pre-cryopreservation 72 hours after thawing. 3) The in dynamic GSIS, the first and the second phase of insulin secretion were well preserved in islets cultured for 72 hours after thawing. 4) The cryopreserved islets were cultured for 3 days and transplanted into renal sub-capsular space of streptozotocin (STZ) induced diabetic rats. The duration of normoglycemia in the STZ-induced diabetic rats transplanted with cryopreserved islets was significantly longer than that of the fresh islets. CONCLUSION: The optimal condition of cryopreservation using the controlled cooling method was established in rat pancreatic islets. This cryopreservation method can be a feasible approach for human islet transplantation.
- Re-transplantation of Pancreatic Islets in Insulin Dependent Diabetes Mellitus.
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Tae Young Yang, Seung Hoon Oh, In Kyung Jeong, In Ah Seo, Eun Young Oh, Gun Young Cho, Sung Joo Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Young Soo Do, Sung Wook Choo
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Korean Diabetes J. 2000;24(4):457-466. Published online January 1, 2001
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Abstract
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Over the past 20 years, significant advances have been made in human islet transplantaiton. However, cases of prolonged insulin independence after islet allotransplantation have rarely been reported and over time, a slight, gradual decrease in insulin secretion appears to occur, as suggested by the lower C-peptide. Although preliminary clinical success achieved over the past few years has been considerably higher with whole pancreatic transplant than with isolated islet grafts, both approaches remain experimental. Islet grafts might gain, over time, increasing credibility and might eventually provide an easier alternative in terms of grafting procedures and patient management, as compared with the more "traumatizing" whole-pancreas transplantation. Also, using islet, re-tran- splantation is possible. But it is not known whether re-transplantation of islet could be suitable for those patients who lost grafted islet function. The aim of the present study was to investigate the benefits of re-transplantation of islet in previously simultaneous islets-kidney transplant(SIK) patient who have lost graft function. METHODS: The recipient was a 32 year old male. First islet transplantation was underwent at December 25, 1999. However, the grafted islets lost function after 70 days. So we performed re-transplantation of islets. The isolation of islet was conducted sterilely on a laminar flow hood and isolated by a modified Recordi method. The islet was injected slowly into the liver via a cannular placed in the potal vein for 20 minutes. RESULTS: Transplanted islets were 90,000 IEq at first islet transplantation, 370,000 IEq at second islet transplantation. The insulin requirement was reduced from 75-85 to 35-40 U/day, the basal C-peptide level was 1.5 ng/mL at 7 days posttransplant Unfortunately, the grafted islets lost function after 70 days. After second transplantation, the insulin requirement was reduced to 26 U/day. CONCLUSIONS: Despite the continuous need for exogenous insulin therapy, islet transplantation can prevent wide glucose fluctuations, thus resulting in norma lization of glycemic control and improvement in HbA1c, and also, show that islets can be successfully and safely re-transplanted intraportally in patients who have lost previously grafted islet function (J Kor Diabetes Asso 457~466, 2000).
- The Stimulatory Effect of IL-1on The Insulin Secretion and Its Relating Factors.
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In Kyung Jeong, Seung Hoon Oh, Tong Mook Kang, Jae Hoon Jeong, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2000;24(4):431-443. Published online January 1, 2001
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Abstract
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The inhibitory effect of IL-1 on the insulin secretion has been validated in pathogenesis of type 1 diabetes, but complex results about the stimulatory effect of IL-1 have been reported. The aims of this study are to clarify the effects of IL-1 on insulin secretion of pancreatic islets and to investigate the mechanisms in terms of preproinsulin synthesis, inducible NOS expression, and calcium channel activity. METHODS: Islets were isolated from male Sprague-Dawley (SD) rat by modified Lacy-Kostianovsky's method. After islets were treated with different concentrations (0, 0.5, 5, 50, 500 pmol/L) and exposure time (2, 6, 24 hours) of IL-1 , morphology, viability, static stimulation of insulin to glucose, insulin content, preproinsulin mRNA expression, iNOS mRNA expression and calcium channel activity were measured. RESULTS: 1) Viability of islets was reduced in high concentrations of long term exposure of IL-1 . 2) Insulin secretion was stimulated in islets treated with 5, 50, and 500 pmol/L of IL-1 for 2 hours and 0.5 pmol/L for 6 hours. It was inhibited in 5, 50, and 500 pmol/L for 6 and 24 hours. 3) Insulin content was not significantly different regardless of concentration and exposure time of IL-1 . 4) Preproinsulin mRNA expression increased in islets treated with 50, 500 pmol/L of IL-1 for 2 hours. After 24 hours, it decreased in dose dependent manner. 5) iNOS mRNA expression was detectable after 2 hours in the presence of IL-1 , peaks at 6 hour and decreased after 24hours. It was increased above 5 pmol/L of IL-1 in dose dependent manner. 6) Activities of the voltage-dependent Ca2+ channels were not different among groups. CONCLUSION: IL-1 plays a positive role in terms of insulin secretion and insulin synthesis in high concentration of short term or low concentration of long term. These effects of IL-1 might be neither dependent of iNOS pathway nor Ca2+ channel activity.
- Distension and Collagenase Digestion Time of The Pancreas are Critical Factors in Islet Isolation of Canine Pancreas.
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Tae Young Yang, In Kyung Jeong, Seung Hoon Oh, Sang Hoon Lee, Dong Jun Kim, Jong Ryul Hahm, Jung Hwan Park, Jong Sung Kim, Jin Soo Han, Sung Joo Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2000;24(2):180-190. Published online January 1, 2001
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Abstract
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S: One of the main problems conditioning the outcome of islet transplantation is the ability to separate a sufficient number of viable islets with preserved function. Islet purification is critically affected by all of the isolation stages, Thus, it is necessary to set up the standard isolation method that islets are separate well from acinar without compromising islet yield and viability. METHODS: Twenty three adult mongrel dogs were used for the experiment of total pancreatectomy with islet isolation. The islets were properly isolated by a modified Recordi method. The obtained islets were further purified by centrifugation on discontinuous gradients using cell separation system (Model 2991, Cobe, Lakewood Colo). We evaluatad islet number (islet equivalent number, 150 gm equivalents/kg of recipient body weight, lEq/kg), purity. cell volume, viabilty, recovery rate, and comparison of outcome according to the isolation conditions. RESULTS: 1) The mean of islet numbers before purification were 13543+/-943 lEq/kg, digestion times were 13.8+/-2.6 min. digestion tamperature was b was 59,7+/-7.0%, viability was 90.0+/-2.1%, cell volume was 4.7+/-1.1 mL, islet number after purification were 4064+/-361 lEq/kg, and recovery rate was 29+2.9. 2) Isolated islet numbers were different according to the degree of pancreas distension with collagenase, digestion temperature, and digestion time. 3) The best conditions for islet isolation were above 37.5 degree C in temperature at recirculation of collagenase, within 12min in digestion time and well distended pancreas with collagenase. 4) According to multiple regression adjusted by variable factors, the degree of pancreas distension with collagenase and digestion time were independently associated factors for successful islet isolation. CONCLUSIONS: In this study, we concluded that the degree of pancreas distension with collagenase and digestion time were independent factors for successful islet isolation and the best conditions for islet isolation were above 37.5 degree C in temperature at recirculation of collagenase, within 12 min in digestion time and well distended pancreas with collagenase.
- Critical Factors Determined Islet Graft Function In Canine Islet Autotransplantation.
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Tae Young Yang, In Kyung Jeong, Seung Hoon Oh, Sang Hoon Lee, Dong Jun Kim, Jong Ryul Hahm, Byung Joon Kim, Kyu Jeung Ahn, Sung Joo Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2000;24(2):170-179. Published online January 1, 2001
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Abstract
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Islet cell transplantation is an attractive alternative to whole organ pancreas transplantation, since it is clearly safer and simpler surgical procedure for the reciplents. However, several obstacles still remain, because the free islets appear to be more susceptible to non-specific inflammatory damage or immune mediated destruction than islets in an intact pancreas. Therefore, the purpose of this study is to examine the functional outcome of islet autograft and the factors related to the islets graft survival in mongrel dogs. METHODS: Twelve adult mongrel dogs weighting 12~16 kg were used for the experiment of total pancratectomy and islet autotransplantation. The islets were properly isolated by a modified Recordi method. The obtained islets were further purified by centrifugation on discontinuous gradients using cell separation system (Model 2991, Cobe, Lakewood Colo). After the heparization(50U/kg), the islets were injected slowly into the liver through the portal vain for 30 minutes. The post-transplantation intravenous glucose tolerence test (IVGTT) with glucose disappearance rate (K), liver function test (LFT), fasting plasma glucose (FPG) ware measured periodically. RESULTS: I) The median of Ks were 1.3%/min (range 0.3~2.1) and the lEq/kg (150 m equivalents/kg of recipient body weight) was 3520 (range 1350-6550). The Ks in recipients with high lEq/kg (> or =5,000) were significantly higher than those in recipients with low lEq/kg (<5,000)(r=0.78, p<0.05). 2) The islet cell viability were estimated to be 95% and the median of the required insulin dosage for the maintenance of normal FPG were 0.7 (range 0~1.6) U/kg/day, The insulin requirement correlated well with the level of lEq/kg (r=-0.90, p<0.01). 3) The median of the volume of the transplanted pancreatic islet cell were 2.1 mL (range 0.7~5.0) and the purity was 60k (range 10~95), The portal pressure gradients of during the transplant procedure were 4.0(range 0.5~12.0) cmH20. The portal pressure gradients in recipients with high purity were significantly lower than those in recipients with low purity (r=-0,80, p<0,05). CONCLUSIONS: In this study, we confirmed that autotransplantation of islet cell on the pancreatectomized dogs can render nearly normoglycemia, and transplanted islet mass was most critical factor to successful autotransplantation in canine model.
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