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

Jens C. Brüning, Dinesh Gautam, Deborah J. Burks, Jennifer Gillette, Markus Schubert, Paul C. Orban, Rüdiger Klein, Wilhelm Krone, Dirk Müller-Wieland, C. Ronald Kahn

doi:10.1126/science.289.5487.2122

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

DOI Web Site 被引用文献50件

Jens C. Brüning

Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine (ZMMK) der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany.
Dinesh Gautam

Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine (ZMMK) der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany.
Deborah J. Burks

Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
Jennifer Gillette

Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine (ZMMK) der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany.
Markus Schubert

Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine (ZMMK) der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany.
Paul C. Orban

European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Rüdiger Klein

European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Wilhelm Krone

Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine (ZMMK) der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany.
Dirk Müller-Wieland

Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine (ZMMK) der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany.
C. Ronald Kahn

Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.

抄録

<jats:p>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.</jats:p>