[HTML][HTML] Tissue-specific knockout of the insulin receptor in pancreatic β cells creates an insulin secretory defect similar to that in type 2 diabetes

RN Kulkarni, JC Brüning, JN Winnay, C Postic… - Cell, 1999 - cell.com
RN Kulkarni, JC Brüning, JN Winnay, C Postic, MA Magnuson, CR Kahn
Cell, 1999cell.com
Dysfunction of the pancreatic β cell is an important defect in the pathogenesis of type 2
diabetes, although its exact relationship to the insulin resistance is unclear. To determine
whether insulin signaling has a functional role in the β cell we have used the Cre-loxP
system to specifically inactivate the insulin receptor gene in the β cells. The resultant mice
exhibit a selective loss of insulin secretion in response to glucose and a progressive
impairment of glucose tolerance. These data indicate an important functional role for the …
Abstract
Dysfunction of the pancreatic β cell is an important defect in the pathogenesis of type 2 diabetes, although its exact relationship to the insulin resistance is unclear. To determine whether insulin signaling has a functional role in the β cell we have used the Cre-loxP system to specifically inactivate the insulin receptor gene in the β cells. The resultant mice exhibit a selective loss of insulin secretion in response to glucose and a progressive impairment of glucose tolerance. These data indicate an important functional role for the insulin receptor in glucose sensing by the pancreatic β cell and suggest that defects in insulin signaling at the level of the β cell may contribute to the observed alterations in insulin secretion in type 2 diabetes.
cell.com