[HTML][HTML] Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes

X Lin, A Taguchi, S Park, JA Kushner… - The Journal of …, 2004 - Am Soc Clin Investig
X Lin, A Taguchi, S Park, JA Kushner, F Li, Y Li, MF White
The Journal of clinical investigation, 2004Am Soc Clin Investig
The molecular link between obesity and β cell failure that causes diabetes is difficult to
establish. Here we show that a conditional knockout of insulin receptor substrate 2 (Irs2) in
mouse pancreas β cells and parts of the brain—including the hypothalamus—increased
appetite, lean and fat body mass, linear growth, and insulin resistance that progressed to
diabetes. Diabetes resolved when the mice were between 6 and 10 months of age:
functional β cells expressing Irs2 repopulated the pancreas, restoring sufficient β cell …
The molecular link between obesity and β cell failure that causes diabetes is difficult to establish. Here we show that a conditional knockout of insulin receptor substrate 2 (Irs2) in mouse pancreas β cells and parts of the brain — including the hypothalamus —increased appetite, lean and fat body mass, linear growth, and insulin resistance that progressed to diabetes. Diabetes resolved when the mice were between 6 and 10 months of age: functional β cells expressing Irs2 repopulated the pancreas, restoring sufficient β cell function to compensate for insulin resistance in the obese mice. Thus, Irs2 signaling promotes regeneration of adult β cells and central control of nutrient homeostasis, which can prevent obesity and diabetes in mice.
The Journal of Clinical Investigation