Role of Brain Insulin Receptor in Control of Body Weight and Reproduction
Abstract
Insulin receptors (IRs) and insulin signaling proteins are widely distributed throughout the central nervous system (CNS). To study the physiological role of insulin signaling in the brain, we created mice with a neuron-specific disruption of the IR gene (NIRKO mice). Inactivation of the IR had no impact on brain development or neuronal survival. However, female NIRKO mice showed increased food intake, and both male and female mice developed diet-sensitive obesity with increases in body fat and plasma leptin levels, mild insulin resistance, elevated plasma insulin levels, and hypertriglyceridemia. NIRKO mice also exhibited impaired spermatogenesis and ovarian follicle maturation because of hypothalamic dysregulation of luteinizing hormone. Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction.
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We thank A. Parlow for the gift of antisera to LH and M. D. Michael for discussions. Supported by grants from the Deutsche Forschungsgemeinschaft (DFG 1492-2 to J.C.B.), the Volkswagenstiftung (to J.C.B., D.M.-W., and W.K.), NIH (DK31036 to C.R.K. and DK55326-01A2 to D.J.B.) and Joslin Diabetes Center Diabetes Endocrinology Research Center grants (to C.R.K. and D.J.B.).
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Science
Volume 289 | Issue 5487
22 September 2000
22 September 2000
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Received: 15 May 2000
Accepted: 3 August 2000
Published in print: 22 September 2000
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- Jens C. Brüning et al.
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