- Efficacy and Safety of Mitiglinide in Korean Type 2 Diabetic Patients: Prospective Randomised Multicenter Comparative Phase III Study.
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Se Young Kim, Hyo Jeong Kim, Kyung Ah Han, Se Hyun Baek, Hyun Sik Son, Bong Soo Cha, Kyung Wan Min
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Korean Diabetes J. 2007;31(2):163-174. Published online March 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.2.163
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Abstract
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- BACKGROUND
Mitiglinide, one of the meglitinides, is expected to prevent postprandial hyperglycemia of type 2 diabetes by enhancing early phase insulin secretion. The aim of this study was to verify the efficacy and safety of mitiglinide compared to nateglinide. METHODS: One hundred eleven of diabetic patients were randomised and administered of mitiglinide (n = 56) and nateglinide (n = 55) before a meal time for 12 weeks. The changes of HbA1c, fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) were analyzed. The safety of this drug was investigated as well. RESULTS: The change of HbA1c was not significantly different between two groups (-0.77 +/- 1.08% in mitiglinide vs. -0.66 +/- 0.79% in nateglinide, P = 0.57). The reduction of FPG (-12.2 +/- 25.0 mg/dL vs. -6.1 +/- 22.3 mg/dL, P = 0.218), PPG 1 hr (-48.0 +/- 47.1 mg/dL, vs. -29.4 +/- 43.2 mg/dL, P = 0.051), and PPG 2 hr (-59.2 +/- 58.0 mg/dL vs. -43.3 +/- 59.0 mg/dL, P = 0.194) were not significantly different between the mitiglinide and the nateglinide, respectively. Drug-related adverse effects were not different between two groups (16.1% in mitiglinide vs. 27.8% in nateglinide, P = 0.137). The frequency of hypoglycemic events were not different between two groups (8.9% in mitiglinide vs. 14.8% in nateglinide, P = 0.339). There were two patients who had complained shoulder pain in the mitiglinide or deterioration of visual acuity in the nateglinide, but those were found to be unrelated with medications. CONCLUSION: This study showed that mitiglinide had reduced HbA1c as similar to nateglinide and that significantly improved HbA1c, FPG and PPG during 12 weeks of treatment. The safety of mitiglinide was also comparable to nateglinide. Mitiglinide could be used as an effective glucose-lowering agent by enhancing early insulin secretion and reducing postprandial glucose excursion, and thereby might contribute long-term cardioprotective effect in Korean type 2 diabetic patients.
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- Monotherapy in Type 2 Diabetes Mellitus Patients 2017: A Position Statement of the Korean Diabetes Association
Sang Youl Rhee The Journal of Korean Diabetes.2018; 19(1): 15. CrossRef - Monotherapy in patients with type 2 diabetes mellitus
Sang Youl Rhee, Hyun Jin Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Kyung Mook Choi, Jin Hwa Kim The Korean Journal of Internal Medicine.2017; 32(6): 959. CrossRef - Monotherapy in Patients with Type 2 Diabetes Mellitus
Sang Youl Rhee, Hyun Jin Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Kyung Mook Choi, Jin Hwa Kim Diabetes & Metabolism Journal.2017; 41(5): 349. CrossRef
- The Effects of High Glucose, Insulin and TGF-beta 1 on Proliferation and Differentiation of the Pancreatic Stellate Cells.
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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
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Korean Diabetes J. 2003;27(3):228-240. Published online June 1, 2003
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- 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.
- 3-Dimensional Long Term Culture of Monolayer Cultured Dispersed Neonatal Porcine Pancreas Cells (NPCC).
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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
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Korean Diabetes J. 2002;26(5):383-395. Published online October 1, 2002
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- 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.
- In Vitro Expansion and Differentiation of Islet Precursor Cells from Cultured Neonatal Porcine Pancreatic Tissue.
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Yu Bae Ahn, Kun Ho Yoon, Sun Hee Seo, Seung Hyun Ko, Ki Ho Song, Je Ho Han, Soon Jip Yoo, Hyun Sik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
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Korean Diabetes J. 2000;24(3):310-322. Published online January 1, 2001
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Abstract
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- BACKGROUND
Neonatal porcine pancreas is an attractive alternative source for islet transplantation because of its growth potential and availability. Porcine neonatal pancreatic cell clusters (NPCCs) consist mainly of protodifferentiated cells expressing both the duct cell marker pancytokeratin and islet hormones. In this study, we investigated to expand and mature the pancreas duct cells contained in porcine NPCCs with extracellular matrix. METHODS: For NPCCs, pancreas obtained from neonatal pigs were minced, digested with collagenase and cultured overnight. Then NPCCs were further dispersed to small cell groups and cultured on HTB-9 extracellular matrix: the tissue attached and formed monolayer patches. At the 3rd and 8th days, tissue was fixed, immunostained for pancytokeratin (panCK), vimentin (VT) and islet hormones. RESULTS: During 5 days culture, the total cell numbers increased 3.2 fold on the matrix, and 1.6 fold on the sticky dish, respectively. Insulin positive cells (Ins+) were 6.0% of total cells at day 3 and increased 1.6 fold in numbers at day 8. There was significant increase in DNA content of NPCCs in monolayers on both sticky dishes and HTB-9 matrix. In contrast, insulin content of both groups decreased during culture periods. Until 8 days of culture after dispersion of porcine NPCC, most duct cells costained with panCK and VT. CONCLUSION: We observed NPCCs were composed of many of duct cells which were known to be endocrine precursor cells and monolayer culture of NPCC withextracellular matrix resulted in the proliferation and differentiation of pancreatic duct cells.
- Prevalence of micro and macroalbuminuria in relation to hypertension and chronic diabetic vascular complications among type II diabeticpatients.
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Hyuk Ho Kwon, Je Ho Han, Jong Min Lee, Soon Jip Yoo, Hyun Sik Son, Kun Ho Yoon, Moo Il Kang, Jwan Soo Hong, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang
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Korean Diabetes J. 1992;16(4):317-324. Published online January 1, 2001
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- No abstract available.
- Effect of calcium upon insulin inhibition induced by hydrocortisonein perfused rat pancreas.
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Kun Ho Yoon, Soon Jib Yoo, Hyun Sik Son, Moo Il Kang, Kwan Soo Hong, Bong Youn Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
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Korean Diabetes J. 1991;15(2):205-212. Published online January 1, 2001
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- No abstract available.
- Relationship between magnesium and calcium to glucose stimulated insulin secretion in the perfused rat pancreas.
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Kun Ho Yoon, Soon Jip Yoo, Hyun Sik Son, Moo Il Kang, Kwan Soo Hong, Bong Youn Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang
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Korean Diabetes J. 1991;15(1):63-71. Published online January 1, 2001
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- No abstract available.
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