Increased expression and activity of 11beta-HSD-1 in diabetic islets and prevention with troglitazone |
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Authors: | Duplomb Laurence Lee Young Wang May-Yun Park Byung H Takaishi Kiyosumi Agarwal Anil K Unger Roger H |
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Affiliation: | Gifford Laboratories, Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. |
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Abstract: | To determine if increased local production of glucocorticoids by the pancreatic islets might play a role in the spontaneous noninsulin-dependent diabetes mellitus of obesity, we compared islet 11beta-HSD-1 mRNA and activity in islets of obese prediabetic and diabetic Zucker Diabetic Fatty (ZDF) (fa/fa) rats and lean wild-type (+/+) controls. In diabetic rat islets, both mRNA and enzymatic activity of the enzyme were increased in proportion to the hyperglycemia. Troglitazone (TGZ) treatment, beginning at 6 weeks of age, prevented the hyperglycemia, the hyperlipidemia, and the increase in 11beta-HSD-1. To determine if the metabolic abnormalities had caused the 11beta-HSD-1 increase, prediabetic islets were cultured in high or low glucose or in 2:1 oleate:palmitate for 3 days. Neither nutrient enhanced the expression of 11beta-HSD-1. We conclude that 11beta-HSD-1 expression and activity are increased in islets of diabetic, but not prediabetic ZDF rats, and that TGZ prevents both the increase in 11beta-HSD-1 and the diabetes. |
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Keywords: | Glucocorticoid 11β-HSD-1 ZDF (fa/fa) rats Islets Cushing’s syndrome and obesity |
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