- Thiazolidinediones on Insulin Resistance and Insulin Secretion in Obese Diabetic OLETF Rats.
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Jung hyun Noh, Seung hyun Hong, Kyoung hee Lee, Kyoung Min Min, Tae young Yang, Myung shik Lee, Kwang won Kim, Moon kyu Lee
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Korean Diabetes J. 2007;31(1):33-43. Published online January 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.1.33
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 Abstract
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- BACKGROUND
Thiazolidinediones are synthetic peroxisome proliferator-activated receptor-gamma agonists that decrease insulin resistance but, as in vitro and in vivo studies suggest, may have direct beneficial effects on pancreatic beta cells. Here, we investigated the effects of thiazolidinediones (TZDs) on the insulin resistance, beta-cell mass and insulin secretion in obese diabetic OLETF rats. METHODS: We studied insulin resistance (by hyperinsulinemic euglycemic clamp) and insulin secretion (by hyperglycemic clamp) in TZDs administered OLETF and LETO rats. Histologic alterations of the islets were observed and beta-cell mass was also measured by point counting method. RESULTS: Chronic administration of troglitazone (TGZ, 0.15%) or pioglitazone (PGZ, 0.02%) prevented the development of glucose intolerance in OLETF rats, as assessed by oral glucose tolerance test. There was significant difference in submaximal glucose infusion rate between TGZ-treated and untreated OLETF rats during euglycemic clamp studies at 24 weeks of age. At 16 and 24 weeks of ages, beta-cell mass significantly increased in TGZ-treated OLETF rats compared to untreated animals. At 19 weeks and 30 weeks of age, first-phase insulin secretion was not different in PGZ-treated OLETF rats from untreated OLETF rats during hyperglycemic clamp study. At 30 weeks of age, late-phase insulin secretion was decreased in PGZ-treated OLETF rats compared to untreated OLETF rats. The expression of alpha-smooth muscle actin, a marker of activated pancreatic stellate cells that are involved in the fibrosis of the pancreas, in the islets was suppressed by TGZ treatment at 24 weeks of age. CONCLUSION: The treatment of TGZ prevented the development of diabetes, and increased insulin sensitivity and pancreatic beta-cell mass in OLETF rats. These results might be related with the suppression of pancreatic stellate cells. Insulin secretion was not affected by PGZ treatment.
- 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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- BACKGROUND
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
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KDA
