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

First Author  Kulkarni RN Year  1997
Journal  J Clin Invest Volume  100
Issue  11 Pages  2729-36
PubMed ID  9389736 Mgi Jnum  J:45259
Mgi Id  MGI:1194705 Doi  10.1172/JCI119818
Citation  Kulkarni RN, et al. (1997) Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. J Clin Invest 100(11):2729-36
abstractText  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.
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