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Endogenous islet uncoupling protein-2 expression and loss of glucose homeostasis in ob/obmice
- Source :
- Journal of Endocrinology; July 2006, Vol. 190 Issue: 3 p659-667, 9p
- Publication Year :
- 2006
-
Abstract
- We hypothesized that the loss of glucose homeostasis in ob/obmice is associated with upregulation of islet uncoupling protein-2 (UCP2) expression, leading to impaired glucose-stimulated insulin secretion (GSIS). Changes in glucose homeostasis in lean and ob/obmice from 5 to 16 weeks were assessed by fasting blood glucose, plasma insulin, oral glucose tolerance, and tissue insulin sensitivity. In vitroGSIS and ATP content were assayed in isolated islets, while UCP2 expression was determined by quantitative real-time PCR and immunoblotting. Short-term reduction of UCP2 expression was achieved through transfection of islets with specific small interfering RNA. Insulin resistance was detected in 5-week-old ob/obmice, but GSIS and blood glucose levels remained normal. By 8 weeks of age, ob/obmice displayed fasting hyperglycemia, hyperinsulinemia and glucose intolerance, and also had elevated non-esterified fatty acid concentration in plasma. In vitro, GSIS and ATP generation were impaired in ob/obislets. Islet UCP2 expression was elevated at 5 and 8 weeks of age. Short-term knockdown of islet UCP2 increased GSIS in islets of lean mice, but had no effect in islets from ob/obmice. Loss of glucose homeostasis and impairment of insulin secretion from isolated islets at 8 weeks in ob/obmice is preceded by an increase in UCP2 expression in islets. Moreover, the glucolipotoxic conditions observed are predicted to increase UCP2 activity, contributing to lower islet ATP and GSIS.
Details
- Language :
- English
- ISSN :
- 00220795 and 14796805
- Volume :
- 190
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Journal of Endocrinology
- Publication Type :
- Periodical
- Accession number :
- ejs46969447
- Full Text :
- https://doi.org/10.1677/joe.1.06715