Central Regulation of Energy Homeostasis
The Key Role of Insulin
- From the Department of Medicine, Division of Endocrinology and Metabolism, University of California San Diego, and the Department of Medicine, Endocrinology, Diabetes and Metabolism Section, VA San Diego Health Care System, San Diego, California
- Address correspondence and reprint requests to Daniel Porte, Jr., MD, 1660 Via Corona, La Jolla, CA 92037. E-mail: dporte{at}ucsd.edu
Abstract
Insulin has two important functions that relate to overall metabolic homeostasis. The phylogenetically oldest is the maintenance of sufficient energy stores to allow for development, growth, and reproduction. The newer is as a feedback regulator of plasma glucose. The key role of the central nervous system in both functions is reviewed from a personal perspective, and the development of the concept that both body weight (adiposity) and plasma glucose are critically regulated by the same hormone is described. The recent suggestion that diabetes and obesity are linked by their common reliance on this central nervous system insulin signaling system is reviewed. Recent efforts to understand the hypothalamic mechanisms involved are described, and the common use of insulin receptor substrate 2 and the phosphatidylinositol 3-kinase signaling mechanism is emphasized. Potential consequences of defects in the secretion of insulin or the action of insulin in the central nervous system are given, and linkage between obesity and diabetes is illustrated with a potential clinical representative.
- AgRP, agouti-related peptide
- CART, cocaine- and amphetamine-related transcript
- CCK, cholecystokinin
- CNS, central nervous system
- GABA, γ-amino butyric acid
- KATP channel, ATP-sensitive K+ channel
- NPY, neuropeptide Y
- PI, phosphatidylinositol
- POMC, proopiomelanocortin
Footnotes
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D.P. holds stock in Abbott, Amcyte, Diamedica, and Merck; has acted as a consultant for Amcyte, Amylin, Bristol-Myers Squibb, Diamedica, Five-Prime Therapeutics, Glaxo-Smith-Kline, Johnson and Johnson, Kowa Research Institute, Mankind Corporation, Merck, Metacure, Novartis, Sankyo, Sanofi-Aventis, and Takeda; and has received honoraria from Amylin and Novartis.
This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted April 21, 2006.
- Received March 24, 2006.
- DIABETES
