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Am J Physiol Endocrinol Metab 278: E1-E14, 2000;
0193-1849/00 $5.00
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Vol. 278, Issue 1, E1-E14, January 2000

INVITED REVIEW
The adipoinsular axis: effects of leptin on pancreatic beta -cells

Timothy J. Kieffer1 and Joel F. Habener2

1 Departments of Medicine and Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; and 2 Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute and Harvard Medical School, Boston, Massachusetts 02114

The prevalence of obesity and related diabetes mellitus is increasing worldwide. Here we review evidence for the existence of an adipoinsular axis, a dual hormonal feedback loop involving the hormones insulin and leptin produced by pancreatic beta -cells and adipose tissue, respectively. Insulin is adipogenic, increases body fat mass, and stimulates the production and secretion of leptin, the satiety hormone that acts centrally to reduce food intake and increase energy expenditure. Leptin in turn suppresses insulin secretion by both central actions and direct actions on beta -cells. Because plasma levels of leptin are directly proportional to body fat mass, an increase of adiposity increases plasma leptin, thereby curtailing insulin production and further increasing fat mass. We propose that the adipoinsular axis is designed to maintain nutrient balance and that dysregulation of this axis may contribute to obesity and the development of hyperinsulinemia associated with diabetes.

insulin secretion; diabetes


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