Role of Brain Insulin Receptor in Control of Body Weight and Reproduction

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Science  22 Sep 2000:
Vol. 289, Issue 5487, pp. 2122-2125
DOI: 10.1126/science.289.5487.2122

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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.

  • * To whom correspondence should be addressed. E-mail: jens.bruening{at} and c.ronald.kahn{at}

  • Present address: San Raffaele Scientific Institute, DIBIT-HSR, Olgettina 60, Milan, Italy.

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