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- Title
Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo.
- Authors
Cases, Jane A.; Gabriely, Ilan; Ma, Xiao Hui; Yang, Xiao Man; Michaeli, Tamar; Fleischer, Norman; Rossetti, Luciano; Barzilai, Nir; Cases, J A; Gabriely, I; Ma, X H; Yang, X M; Michaeli, T; Fleischer, N; Rossetti, L; Barzilai, N
- Abstract
The demonstration of leptin receptors on the pancreatic beta-cells suggests the possibility of direct actions of leptin on insulin secretion. In vitro studies on islets or perfused pancreas and beta-cell lines produced inconsistent results. We performed an in vivo study to distinctly examine whether leptin has an effect on glucose-stimulated insulin secretion. Young chronically catheterized Sprague-Dawley rats (n = 28) were subjected to a 4-h hyperglycemic clamp study (approximately 11 mmol/l). At minute 120 to 240, rats were assigned to receive either saline or leptin (0.1, 0.5, and 5 microg x kg(-1) x min) infusion. Leptin decreased plasma insulin levels abruptly, and an approximately twofold decrease in plasma insulin levels compared with saline control was sustained over the 2 h of the study (14.8 +/- 5.8 vs. 34.8 +/- 2.6 ng/ml with leptin and saline infusion, respectively, P < 0.001). Moreover, a dose-dependent decrease in plasma insulin levels was noted (r = -0.731, P < 0.01). Since milrinone, an inhibitor of cAMP phosphodiesterase (PDE) 3, did not reverse the effect of leptin on glucose-induced insulin secretion, its action may be independent of PDE3. These findings suggest that acute physiological increase in plasma leptin levels acutely and significantly inhibits glucose-stimulated insulin secretion in vivo. The site of leptin effects on insulin secretion remains to be determined.
- Subjects
INSULIN; LEPTIN; GLUCOSE; PANCREATIC secretions; PEPTIDE hormones
- Publication
Diabetes, 2001, Vol 50, Issue 2, p348
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.50.2.348