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 language | English (US) |
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Pages (from-to) | 594-599 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 313 |
Issue number | 3 |
DOIs | |
State | Published - 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