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Leptin Affects Pancreatic Endocrine Functions through the Sympathetic Nervous System¹

Department of Laboratory Medicine, School of Medicine, the University of Tokushima, Tokushima 770-8503, Japan

Address all correspondence and requests for reprints to: Kenji Shima, M.D., Ph.D., Department of Laboratory Medicine, School of Medicine, the University of Tokushima, Kuramotocho 3-chome, Tokushima 770-8503, Japan. E-mail: shima{at}clin.med.tokushima-u.ac.jp

The effects of leptin on the secretion of insulin and glucagon were examined. In an experiment involving insulin response to an iv glucose load in vagotomized rats, the plasma concentrations of insulin were significantly lower in the leptin (20 nmol/kg BW)-treated group than in a control group. However, in intact rats and rats that had undergone both vagotomy and chemical sympathectomy, this suppressive effect of leptin on insulin secretion was not detected. In an experiment involving a hypoglycemia-induced glucagon secretion test in intact rats, an iv injection of leptin (20 nmol/kg BW) augmented the plasma glucagon response to hypoglycemia. In the case of sympathectomized rats, however, this stimulative effect of leptin on glucagon secretion was not detected. In an experiment with perfused rat pancreas, the addition of leptin (20 nM) to the perfusate slightly suppressed insulin secretion, but had no effect on basal or glucopenia-induced glucagon secretion. In intact rats infused with leptin (0.31 µmol/day), the expression of uncoupling protein-1 messenger RNA in interscapular brown adipose tissue was increased, whereas no such effect of leptin on the uncoupling protein-1 messenger RNA expression was observed in brown adipose tissue in chemically sympathectomized rats. These findings suggest that leptin might indirectly affect pancreatic endocrine functions, probably through its stimulative effects on the sympathetic nervous system.

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