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

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 i...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2000-09, Vol.289 (5487), p.2122-2125
Main Authors: Brüning, Jens C., Gautam, Dinesh, Burks, Deborah J., Gillette, Jennifer, Schubert, Markus, Orban, Paul C., Klein, Rüdiger, Krone, Wilhelm, Müller-Wieland, Dirk, Kahn, C. Ronald
Format: Article
Language:English
Subjects:
Adipose Tissue
Anatomy
Animal reproduction
Animals
Biological and medical sciences
Blood Glucose - analysis
Body fat
Body Weight
Brain
Brain - metabolism
Central nervous system
Central neurotransmission. Neuromudulation. Pathways and receptors
Degeneration
Eating
Female
Female animals
Females
Fundamental and applied biological sciences. Psychology
Genotypes
Germ cells
Hypertriglyceridemia - etiology
Individualized Instruction
Insulin
Insulin - blood
Insulin - physiology
Insulin Resistance
IR gene
Leptin - blood
Leuprolide - pharmacology
Luteinizing Hormone - blood
Male
Male animals
Males
Mice
Mice, Knockout
Nerve degeneration
Nervous system
Neurons
Neurons - metabolism
Obesity
Obesity - etiology
Ovarian Follicle - physiology
Physiological aspects
Receptor, Insulin - genetics
Receptor, Insulin - physiology
Reproduction
Rodents
Scientific Concepts
Sex Characteristics
Signal Transduction
Spermatogenesis
Stem cells
Vertebrates: nervous system and sense organs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.289.5487.2122