- Effects of Anti-Vascular Endothelial Growth Factor (VEGF) on Pancreatic Islets in Mouse Model of Type 2 Diabetes Mellitus.
-
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
-
Korean Diabetes J. 2009;33(3):185-197. Published online June 1, 2009
-
DOI: https://doi.org/10.4093/kdj.2009.33.3.185
-
-
Abstract
PDF
- 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.
- 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
-
-
2,653
View
-
34
Download
-
2
Crossref
-
Abstract
PDF
- 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.
-
Citations
Citations to this article as recorded by
- 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
- Glucose-dependent Insulin Secretion from Genetically Engineered K-cells Using EBV-based Episomal Vector.
-
Ju Hee Kim, Sung Dae Moon, Seung Hyun Ko, Yu Bai Ahn, Ki Ho Song, Hyang Sook Lim, Sook Kyung Lee, Soon Jip Yoo, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Sung Joo Kim, Je Ho Han
-
Korean Diabetes J. 2007;31(1):9-21. Published online January 1, 2007
-
DOI: https://doi.org/10.4093/jkda.2007.31.1.9
-
-
2,665
View
-
20
Download
-
2
Crossref
-
Abstract
PDF
- BACKGROUND
Type 1 diabetes mellitus is an autoimmune disease resulting in destruction of the pancreatic beta cells. Insulin gene therapy for these patients has been vigorously researched. The strategy for achieving glucose-dependent insulin secretion in gene therapy relies on glucose-responsive transcription of insulin mRNA and the constitutive secretory pathway of target non-beta cells. We observed that genetically engineered K-cells using Epstein-Barr virus (EBV)-based episomal vector can produce glucose-regulated insulin production. METHODS: Green fluorescent protein (GFP) or rat-preproinsulin (PPI) expression cassette transcriptionally controlled by the promoter of glucose dependent insulinotropic peptide (GIPP) is fused to pCEP4 containing the origin of replication (oriP) and Epstein-Barr virus nuclear antigen 1 (EBNA-1). CMV promoter was replaced by subcloning the GIPP into pCEP4 to generate pGIPP/CEP4. Two recombinant EBV-based episomal vectors, pGIPP/GFP/CEP4 and pGIPP/PPI/CEP4, were constructed. pGIPP/GFP/CEP4 and pGIPP/PPI/CEP4 containing K-cell specific GIPP were co-transfected into STC-1. K-cell was isolated from the clonal expansion of the fluorescent cells selected by hygromycin treatment in STC-1, and were analyzed for the expression of glucokinase (GK) or transcription factors involved in pancreas development. K-cells concurrently transfected with pGIPP/PPI/CEP4 and pGIPP/GFP/CEP4 were analyzed for the transcripts of PPI by RT-PCR, and for the glucose dependent insulin expression by immunocytochemistry or insulin assay using ultra-sensitive rat-specific insulin ELISA kit. RESULT: STC-1 was stably-transfected with pGIPP/GFP/CEP4 along with pGIPP/PPI/CEP4. Genetically selected fluorescent K-cells expressed GK and transcription factors involved in pancreas development. And K-cells transfected with pGIPP/PPI/CEP4 contained detectable levels of PPI transcripts and showed glucose-dependent immunoreactive insulin secretion. CONCLUSION: We identified genetically engineered K-cells which exert a glucose-dependent insulin expression using EBV-based episomal vector. The similarities between K-cells and pancreatic beta cells support that K-cells may make effective and ideal targeting cells for insulin gene therapy or alternative cell therapy.
-
Citations
Citations to this article as recorded by
- Relationship of traditional and nontraditional cardiovascular risk factors to coronary artery calcium in type 2 diabetes
Ju-Yeon Sim, Ju-Hee Kim, Yu-Bae Ahn, Ki-Ho Song, Je-Ho Han, Bong-Yun Cha, Sook-Kyung Lee, Sung-Dae Moon Korean Diabetes Journal.2009; 33(6): 466. CrossRef - Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells
Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Sung-Dae Moon, Ki-Ho Song Korean Diabetes Journal.2009; 33(6): 475. CrossRef
- Inducible Nitric Oxide Synthase (iNOS) Expression in the Hypoxic Injury to Pancreatic Beta (MIN6) Cells.
-
Seung Hyun Ko, Seung Bum Kim, Kyung Ryul Ryu, Ji Won Kim, Yu Bai Ahn, Sung Dae Moon, Sung Rae Kim, Jung Min Lee, Hyuk Snag Kwon, Kun Ho Yoon, Ki Ho Song
-
Korean Diabetes J. 2006;30(5):336-346. Published online September 1, 2006
-
DOI: https://doi.org/10.4093/jkda.2006.30.5.336
-
-
Abstract
PDF
- BACKGROUND
Islet transplantation is an alternative potential strategy to cure type 1 diabetes mellitus. However, two or more donors are usually needed for one recipient because a substantial part of the graft becomes nonfunctional due to several factors including hypoxia. Though hypoxic exposure of pancreatic beta cells has been reported to induce apoptotic cell death, the molecular processes involved in hypoxia-induced cell death are poorly understood. In type I diabetes, Nitric Oxide (NO) is known as an important cytokine, involved in the pathogenesis of beta cell dysfunction. Pancreatic beta cells are sensitive to the induction of inducible nitric oxide synthase (iNOS) when stimulated by TNF-a or IL-1beta. But contribution of iNOS in response to hypoxia is not yet fully understood. METHODS: Mouse insulinoma cells (MIN6) were incubated in an anaerobic chamber (75% N2/15% CO2/5% H2) for up to 12 hours. Cell viability was measured after AO/PI staining. Caspase-3 activation was also determined using Western blot analysis. Nitric Oxide (NO) release into culture medium was measured using a Griess reagent. The expression of iNOS and PDX-1 mRNA and iNOS protein was examined using real time PCR and Western blot analysis. RESULTS: Marked cell death was observed within 6 hours after hypoxic exposure of MIN6 cells (control, < 5%; 2 hr, 11.0+/-7.6%; 6 hr, 46.2+/-12.8%, P < 0.05). Immunoreactivity to activated caspase-3 was observed at 2, 4 and 6 hrs. NO production was increased in a time dependent manner. Expression of iNOS mRNA and protein was significantly increased at 4 and 6 hour after hypoxia. iNOS expression was confirmed by immunostaining. Of note, Pdx-1 mRNA expression was markedly attenuated by hypoxic treatment. Pretreatment with a selective iNOS inhibitor, 1400 W, significantly prevented beta cell death induced by hypoxic injury. CONCLUSION: Our data suggest that iNOS-NO play an important role in hypoxic injury to MIN6 cells. Therefore, iNOS-NO might be a potential therapeutic target for improving engraftment of the transplanted islets and suppression of iNOS would be helpful for prevention of beta cells damage to hypoxic injury.
- 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
-
-
2,831
View
-
37
Download
-
6
Crossref
-
Abstract
PDF
- 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.
-
Citations
Citations to this article as recorded by
- 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 Diabetes & Metabolism Journal.2017; 41(4): 275. CrossRef - Screening of Autonomic Neuropathy in Patients with Type 2 Diabetes
Bo Kyung Koo Diabetes & Metabolism Journal.2014; 38(5): 346. CrossRef - Decision trees and multi-level ensemble classifiers for neurological diagnostics
Herbert F. Jelinek, Jemal H. Abawajy, Andrei V. Kelarev, Morshed U. Chowdhury, Andrew Stranieri AIMS Medical Science.2014; 1(1): 1. CrossRef - Correlation between Predictors for Diabetic Gastroparesis and Gastric Emptying Scintigraphy
Kyung-Ju Lee, Kyoung-Ho Ryu, Jin-Ook Chung, Dong-Hyeok Cho, Dong-Jin Chung, Min-Young Chung Chonnam Medical Journal.2009; 45(3): 175. CrossRef - Epidemiologic Characteristics of Diabetes Mellitus in Korea: Current Status of Diabetic Patients Using Korean Health Insurance Database
Ie Byung Park, Sei Hyun Baik Korean Diabetes Journal.2009; 33(5): 357. CrossRef - The Status of Diabetes Mellitus and Effects of Related Factors on Heart Rate Variability in a Community
Kyeong-Soon Chang, Kwan Lee, Hyun-Sul Lim Korean Diabetes Journal.2009; 33(6): 537. CrossRef
- Pancreatic Stellate Cell Activation by High Glucose and Its Effect on Angiotensin II.
-
Seung Hyun Ko, Oak Kee Hong, Min Kyung Lee, Eun He Park, Sung Soo Lee, Yu Bai Ahn, Ki Ho Song, Bong Yun Cha, Ho Young Son, Myung Jun Kim, In Kyung Jung, Kun Ho Yoon
-
Korean Diabetes J. 2005;29(4):304-314. Published online July 1, 2005
-
-
-
Abstract
PDF
- BACKGROUND
Pancreatic stellate cells (PSCs) are known to be related to pancreatic inflammation and fibrosis, and are the result of extracellular matrix(ECM) protein synthesis. Recent studies have shown that blockade of the renin-angiotensin system (RAS) attenuated pancreatic inflammation and fibrosis. However, there is little data relating to high glucose (HG) and its effects on PSCs. We investigated the effects of HG on ECM protein and angiotensin II(AT II) in PSCs. METHODS: Isolated PSCs were cultured in HG(D-glucose 5.5(LG), 27.8 mM(HG)) medium. The levels of AT II and TGF-beta were measured using radioimmunoassay, and the AT II-stained cells counted. RT-PCR for the AT II receptor subtypes and Western blot analyses for the expressions of ECM proteins, such as connective tissue growth factor(CTGF) and collagen type IV, were performed. The AT II receptor antagonist, candesartan(10micrometer), and angiotensin converting enzyme inhibitor, ramiprilat(100nM) treatedments were also used. RESULTS: The thymidine uptake of the PSCs increased 4 times in the HG culture. The AT II levels(LG vs. HG, 17.1+/-4.9 vs. 36.0+/-.2pg/mL, P<0.05) and AT II-stained PSCs (LG vs. HG, 22.5+/-2.0 vs. 39.3+/-11.0%, P<0.05) were significantly increased after 6 hrs under HG conditions. The TGF-beta concentration was also significantly higher under HG conditions(LG vs. HG, 436.3+/-69.0 vs. 1115.1+/-434.0pg/mL, P<0.05) after 72 hrs. After 72 hrs, the protein expressions of CTGF and collagen type IV under HG conditions were significantly increased and effectively attenuated by the candesartan and ramiprilat treatments. CONCLUSION: A high glucose concentration could significantly increased PSCs proliferation, which also correlated with the AT II production. Consequently, PSCs proliferation was caused by HG induced ECM protein synthesis, and was attenuated by the AT II receptor antagonist. Therefore, pancreatic inflammation and fibrosis could be aggravated by hyperglycemia, and AT II might play an important role in the pathogenesis.
- The Long-term Effect of a Structured Diabetes Education Program for Uncontrolled Type 2 Diabetes Mellitus Patients-a 4-Year Follow-up.
-
Min Sun Song, Ki Ho Song, Seung Hyun Ko, Yu Bai Ahn, Joon Sung Kim, Jin Hee Shin, Yang Kyung Cho, Kun Ho Yoon, Bong Youn Cha, Ho Young Son, Dong Han Lee
-
Korean Diabetes J. 2005;29(2):140-150. Published online March 1, 2005
-
-
-
Abstract
PDF
- BACKGROUND
Diabetes mellitus is a chronic illness with many metabolic complications. The prevalence of diabetes mellitus has markedly increased. Until now, however, little data have been presented for the long-term evaluation of a structured diabetes education program (SDEP) for patients with type 2 diabetes mellitus. The aim of this study was to examine the effects of the SDEP on glycemic control, lipid profiles, and self-care behavior over a four-year follow-up period. METHODS: A total of 248 diabetic patients completed the SDEP from December 1999 to September 2000. Ninety-eight patients were followed-up for more than four years and 75 of them were selected for the study, after those subjects having a baseline glycated hemoglobin(HbA1c) levels below 7.9% were excluded. The laboratory data included the glycemic control status(fasting blood sugar and HbA1c), serum creatinine, and lipid profiles. Compliance with their diet, self monitoring of blood glucose, and their exercise frequency were monitored with a questionnaire that was completed by the patients when they visited the hospital. The data were analyzed by using repeated ANOVA measures and chi2 testing for detecting trends. RESULTS: There were no significant decreases in the fasting blood glucose, creatinine, total cholesterol, triglycerides or low density lipoprotein cholesterol for the SDEP group compared with the control group. The self-care behavior of the SDEP group was much better than that of the control group and it was well maintained. Although the self-care behavior tended to deteriorate with time in the SDEP group, the exercise frequency did not change. The HbA1c level was much improved in the SDEP group(HbA1c: SDEP, 7.9+/-1.2% vs. 8.9+/-1.6% for the control; P =0.009). High density lipoprotein(HDL) cholesterol was also relatively improved in the SDEP group(HDL cholesterol: SDEP, 1.1+/-0.2 mmol/L vs. 1.0+/-0.3mmol/L for the control; P=0.006). CONCLUSIONS: The glycemic control status of diabetic patients who undertook the SDEP was satisfactory for one year after the program, although all the habitual compliance measures decreased gradually with time over the total four years. These results demonstrate that the SDEP for patients with diabetes is useful in improving their long-term glycemic control and self-care behavior. Regular and sustained reinforcement with encouragement will be required for the diabetic patients to maintain their self-care
- A Case of Necrobiosis Lipoidica at the Insulin Injection Site in a Patient with Type 2 Diabetes Mellitus.
-
Woo Tae Kim, Tae Hoon Kim, Se Min Lee, Kang Hyun Choi, Seung Hyun Ko, Yu Bai Ahn, Ki Ho Song, Ho Young Son, Kyung Moon Kim, Si Young Kim
-
Korean Diabetes J. 2004;28(5):452-457. Published online October 1, 2004
-
-
-
Abstract
PDF
- Nearly one third of patients with diabetes mellitus have some kinds of dermatologic complication. Necrobiosis lipoidica (NL) is a rare degenerative disease of the collagen in the dermis occurring in 0.3~0.7% of the diabetic population. This is a dermatologic condition presenting plaques that have an erythematous, violaceous border and yellowish atrophic center with telangiectasis on its surface. One third of these lesions may progress to ulcer if exposed to any trauma. There is some controversy regarding the degree of association between NL and diabetes mellitus. Necrobiosis lipoidica is commonly seen in patients with type 1 diabetes, but 7~30% of diabetic patients with NL have type 2 diabetes. We report a case of 54 year-old woman with 25 years of diabetic history. Her skin lesion was oval or irregular indurated plaques with central atrophy occurring both arm, lower abdomen and both anterior thigh, especially at insulin injecton site. We focused glycemic control as a treatment and used antiplatelet agents such as aspirin and cilostazol on the basis of microangiopathic athophysiology, combined with antibiotics. We need to inspect more closely any of skin lesions in diabetic patients, thus misdiagnosis and improper treatment should be reduced.
|