[HTML][HTML] Transgenic rescue of insulin receptor–deficient mice

H Okamoto, J Nakae, T Kitamura… - The Journal of …, 2004 - Am Soc Clin Investig
H Okamoto, J Nakae, T Kitamura, BC Park, I Dragatsis, D Accili
The Journal of clinical investigation, 2004Am Soc Clin Investig
The role of different tissues in insulin action and their contribution to the pathogenesis of
diabetes remain unclear. To examine this question, we have used genetic reconstitution
experiments in mice. Genetic ablation of insulin receptors causes early postnatal death from
diabetic ketoacidosis. We show that combined restoration of insulin receptor function in
brain, liver, and pancreatic β cells rescues insulin receptor knockout mice from neonatal
death, prevents diabetes in a majority of animals, and normalizes adipose tissue content …
The role of different tissues in insulin action and their contribution to the pathogenesis of diabetes remain unclear. To examine this question, we have used genetic reconstitution experiments in mice. Genetic ablation of insulin receptors causes early postnatal death from diabetic ketoacidosis. We show that combined restoration of insulin receptor function in brain, liver, and pancreatic β cells rescues insulin receptor knockout mice from neonatal death, prevents diabetes in a majority of animals, and normalizes adipose tissue content, lifespan, and reproductive function. In contrast, mice with insulin receptor expression limited to brain or liver and pancreatic β cells are rescued from neonatal death, but develop lipoatrophic diabetes and die prematurely. These data indicate, surprisingly, that insulin receptor signaling in noncanonical insulin target tissues is sufficient to maintain fuel homeostasis and prevent diabetes.
The Journal of Clinical Investigation