Increased expression and activity of 11β-HSD-1 in diabetic islets and prevention with troglitazone

Laurence Duplomb, Young H Lee, May-Yun Wang, Byung H. Park, Kiyosumi Takaishi, Anil K Agarwal, Roger H Unger

Research output: Contribution to journalArticle

34 Scopus citations

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 11β-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 11β-HSD-1. To determine if the metabolic abnormalities had caused the 11β-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 11β-HSD-1. We conclude that 11β-HSD-1 expression and activity are increased in islets of diabetic, but not prediabetic ZDF rats, and that TGZ prevents both the increase in 11β-HSD-1 and the diabetes.

Original languageEnglish (US)
Pages (from-to)594-599
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume313
Issue number3
DOIs
StatePublished - Jan 16 2004

Keywords

  • 11β-HSD-1
  • Cushing's syndrome and obesity
  • Glucocorticoid
  • Islets
  • ZDF (fa/fa) rats

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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