Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo

Jane A. Cases, Ilan Gabriely, Xiao Hui Ma, Xiao Man Yang, Tamar Michaeli, Norman Fleischer, Luciano Rossetti, Nir Barzilai

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


The demonstration of leptin receptors on the pancreatic β-cells suggests the possibility of direct actions of leptin on insulin secretion. In vitro studies on islets or perfused pancreas and β-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 (∼ 11 mmol/l). At minute 120 to 240, rats were assigned to receive either saline or leptin (0.1, 0.5, and 5 μg · kg-1 · 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.

Original languageEnglish (US)
Pages (from-to)348-352
Number of pages5
Issue number2
StatePublished - 2001

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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