Premium
Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms
Author(s) -
Muzumdar Radhika,
Ma Xiaohui,
Yang Xiaoman,
Atzmon Gil,
Bernstein Julia,
Karkanias George,
Barzilai Nir
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0991fje
Subject(s) - leptin , medicine , endocrinology , melanocortin , insulin , leptin receptor , saline , melanocortin receptor , receptor , chemistry , obesity
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 (∼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 ∼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 β‐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.