Optimal elevation of β-cell 11β-hydroxysteroid dehydrogenase type 1 is a compensatory mechanism that prevents high-fat diet-induced β-cell failure.

ABSTRACT: Type 2 diabetes ultimately results from pancreatic β-cell failure. Abnormally elevated intracellular regeneration of glucocorticoids by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in fat or liver may underlie pathophysiological aspects of the metabolic syndrome. Elevated 11β-HSD1 is also found in pancreatic islets of obese/diabetic rodents and is hypothesized to suppress insulin secretion and promote diabetes. To define the direct impact of elevated pancreatic β-cell 11β-HSD1 on insulin secretion, we generated β-cell-specific, 11β-HSD1-overexpressing (MIP-HSD1) mice on a strain background prone to β-cell failure. Unexpectedly, MIP-HSD1(tg/+) mice exhibited a reversal of high fat-induced β-cell failure through augmentation of the number and intrinsic function of small isle

SUBMITTER: Turban S 

PROVIDER: S-EPMC3282808 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature