Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice

Rohit N. Kulkarni, Zhi Li Wang, Ren Ming Wang, James D. Hurley, David M. Smith, Mohammad A. Ghatei, Dominic J. Withers, James V. Gardiner, Cliff J. Bailey, Stephen R. Bloom*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Obesity is associated with diabetes, and leptin is known to be elevated in obesity. To investigate whether leptin has a direct effect on insulin secretion, isolated rat and human islets and cultured insulinoma cells were studied. In all cases, mouse leptin inhibited insulin secretion at concentrations within the plasma range reported in humans. Insulin mRNA expression was also suppressed in the cultured cells and rat islets. The long form of the leptin receptor (OB-Rb) mRNA was present in the islets and insulinoma cell lines. To determine the significance of these findings in vivo, normal fed mice were injected with two doses of leptin. A significant decrease in plasma insulin and associated rise in glucose concentration were observed. Fasted normal and leptin receptor-deficient db/db mice showed no response to leptin. A dose of leptin, which mimicked that found in normal mice, was administered to leptin-deficient, hyperinsulinemic ob/ob mice. This caused a marked lowering of plasma insulin concentration and a doubling of plasma glucose. Thus, leptin has a powerful acute inhibitory effect on insulin secretion. These results suggest that the action of leptin may be one mechanism by which excess adipose tissue could acutely impair carbohydrate metabolism.

Original languageEnglish
Pages (from-to)2729-2736
Number of pages8
JournalJournal of Clinical Investigation
Volume100
Issue number11
Publication statusPublished - 1 Dec 1997

Keywords

  • β cells
  • Insulin
  • Islet
  • Leptin
  • Suppression

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