Rn. Kulkarni et al., Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes, CELL, 96(3), 1999, pp. 329-339
Dysfunction of the pancreatic beta cell is an important defect in the patho
genesis of type 2 diabetes, although its exact relationship to the insulin
resistance is unclear. To determine whether insulin signaling has a functio
nal role in the beta cell we have used the Cre-loxP system to specifically
inactivate the insulin receptor gene in the beta 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 importa
nt functional role for the insulin receptor in glucose sensing by the pancr
eatic beta cell and suggest that defects in insulin signaling at the level
of the beta cell may contribute to the observed alterations in insulin secr
etion in type 2 diabetes.