We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
β-cell?specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter β-cell mass.
- Authors
Kulkarni, Rohit N.; Holzenberger, Martin; Shih, David Q.; Ozcan, Umut; Stoffel, Markus; Magnuson, Mark A.; Kahn, C. Ronald
- Abstract
Regulation of glucose homeostasis by insulin depends on the maintenance of normal β-cell mass and function. Insulin-like growth factor 1 (Igf1) has been implicated in islet development and differentiated function, but the factors controlling this process are poorly understood. Pancreatic islets produce Igf1 and Igf2, which bind to specific receptors on β-cells. Igf1 has been shown to influence β-cell apoptosis, and both Igf1 and Igf2 increase islet growth; Igf2 does so in a manner additive with fibroblast growth factor 2 (ref. 10). When mice deficient for the Igf1 receptor (Igf1r[sup +/-]) are bred with mice lacking insulin receptor substrate 2 (Irs2[sup -/-]), the resulting compound knockout mice show a reduction in mass of β-cells similar to that observed in pancreas of Igf1r[sup -/-] mice (ref. 11), suggesting a role for Igf1r in growth of β-cells. It is possible, however, that the effects in these mice occur secondary to changes in vascular endothelium 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 β-cell-specific knockout of Igf1r (βlgf1r[sup -/-]). These mice show normal growth and development of β-cells, but have reduced expression of Slc2a2 (also known as Glut2) and Gck (encoding glucokinase) in β-cells, which results in defective glucose-stimulated insulin secretion and impaired glucose tolerance. Thus, Igf1r is not crucial for islet β-cell development, but participates in control of differentiated function.
- Publication
Nature Genetics, 2002, Vol 31, Issue 1, p111
- ISSN
1061-4036
- Publication type
Academic Journal
- DOI
10.1038/ng872