Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms.

Radhika Muzumdar, Xiaohui Ma, Xiaoman Yang, Gil Atzmon, Julia Bernstein, George Karkanias, Nir Barzilai

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Abstract

Leptin has been shown to decrease glucose-stimulated insulin secretion in both in vivo and in vitro studies. As some of the effects of leptin have been elicited through both peripheral and central mechanisms, we assessed whether leptin modulates insulin secretion also through the central nervous system. We infused leptin or saline through implanted intracerebro-ventricular (ICV) catheters to chronically catheterized, conscious rats (n=15), 2 h after initiation of hyperglycemic (approximately 11 mM) clamp. On ICV administration of leptin, there was a gradual and progressive decrease in plasma insulin levels by 52% with 30 ng (P<0.005) and by 28% with 20 ng (P<0.05) of leptin compared with ICV saline. The effect of 20 ng leptin ICV was replicated by intravenous (IV) leptin infusion that achieved physiological leptin levels of approximately 17 ng/ml (n=5). When the melanocortin (MC) pathway was blocked with a nonselective MC-3/4 antagonist SHU 9119 administered ICV, and either saline or leptin (n=12) was infused IV, intravenous leptin failed to produce a decrease in glucose-stimulated insulin levels. We conclude that leptin decreases insulin levels by a predominantly central mechanism, probably via the melanocortin receptors; and peripheral leptin receptors on the beta-cells do not play a major role. The physiological features of this response suggest a possible role for leptin in the evolution of diabetes in overweight individuals.

Original languageEnglish (US)
Pages (from-to)1130-1132
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number9
StatePublished - 2003

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Leptin
Insulin
Melanocortins
Melanocortin Receptors
Leptin Receptors
Glucose
Catheters
Clamping devices
Neurology
Medical problems
Intravenous Infusions
Rats
Central Nervous System

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Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms. / Muzumdar, Radhika; Ma, Xiaohui; Yang, Xiaoman; Atzmon, Gil; Bernstein, Julia; Karkanias, George; Barzilai, Nir.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 17, No. 9, 2003, p. 1130-1132.

Research output: Contribution to journalArticle

Muzumdar, Radhika ; Ma, Xiaohui ; Yang, Xiaoman ; Atzmon, Gil ; Bernstein, Julia ; Karkanias, George ; Barzilai, Nir. / Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms. In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2003 ; Vol. 17, No. 9. pp. 1130-1132.
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AU - Karkanias, George

AU - Barzilai, Nir

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