Regulation of glucose homeostasis by insulin depends on the maintenance of normal -cell mass and function. Insulin-like growth factor 1 (Igf1) has been implicated in islet development and differentiated function1,
2, but the factors controlling this process are poorly understood. Pancreatic islets produce Igf1 and Igf2, which bind to specific receptors on -cells3,
4,
5,
6. Igf1 has been shown to influence -cell apoptosis7, and both Igf1 and Igf2 increase islet growth8,
9; Igf2 does so in a manner additive with fibroblast growth factor 2 (ref. 10). When mice deficient for the Igf1 receptor (Igf1r+/-) are bred with mice lacking insulin receptor substrate 2 (Irs2-/-), the resulting compound knockout mice show a reduction in mass of -cells11 similar to that observed in pancreas of Igf1r-/- mice (ref. 11), suggesting a role for Igf1r in growth of -cells. It is possible, however, that the effects in these mice occur secondary to changes in vascular endothelium12 or in the pancreatic ductal cells, or because of a decrease in the effects of other hormones implicated in islet growth. To directly define the role of Igf1, we have created a mouse with a -cell−specific knockout of Igf1r (Igf1r-/-). These mice show normal growth and development of -cells, but have reduced expression of Slc2a2 (also known as Glut2) and Gck (encoding glucokinase) in -cells, which results in defective glucose-stimulated insulin secretion and impaired glucose tolerance. Thus, Igf1r is not crucial for islet -cell development, but participates in control of differentiated function.
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-cell−specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter 
-cell mass and function. Insulin-like growth factor 1 (Igf1) has been implicated in islet development and differentiated function
-cell development and peripheral insulin signalling
