jci.org
J Clin Invest, October 2001, Volume 108, Number 7, 963-964
Copyright ©2001 by the American Society for Clinical Investigation
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Commentary
Progress in the search for neuronal mechanisms coupling type 2 diabetes to obesity
Michael W. Schwartz
Division of Metabolism, Endocrinology and Nutrition, University of Washington, Harborview Medical Center, 325 Ninth Avenue, Box 359757, Seattle, Washington 98104-2499, USA.
Phone: (206) 341-5288; Fax: (206) 341-5293; E-mail: mschwart@u.washington.edu.
Obesity, insulin resistance, and type 2 diabetes are a tightly linked and increasingly common triad of metabolic disorders. A well-supported and widely accepted explanation for their association is that obesity-induced insulin resistance in tissues such as muscle, liver, and fat increases the demand for insulin, and that type 2 diabetes ensues when this heightened demand cannot be met by defective pancreatic ß cells. Despite the undeniable importance of adipocytes in the regulation of insulin sensitivity (see refs. 1-3 for recent reviews and insights into this interaction), this understanding of the pathogenesis of type 2 diabetes may yet be incomplete. Growing evidence suggests that the CNS plays a key role in glucose homeostasis, via brain pathways that overlap with those controlling food intake and body weight. Advancing this notion a step further is the study by Obici et al., published in this issue of the JCI (4), implicating a specific hypothalamic neuronal pathway — the melanocortin pathway — in the control of insulin sensitivity in peripheral tissues. The recognition that neuronal melanocortin signaling also figures prominently in energy homeostasis, the process whereby energy intake is matched to energy expenditure over time, suggests an intimate coupling of neuronal mechanisms regulating body weight and glucose metabolism (Figure 1). Disorders affecting key neuronal pathways can therefore be included among potential mechanisms linking obesity to type 2 diabetes (5). <snip> |
