| First Author | Rajkumar K | Year | 1996 |
| Journal | Am J Physiol | Volume | 270 |
| Issue | 4 Pt 1 | Pages | E565-71 |
| PubMed ID | 8928760 | Mgi Jnum | J:32700 |
| Mgi Id | MGI:80188 | Doi | 10.1152/ajpendo.1996.270.4.E565 |
| Citation | Rajkumar K, et al. (1996) Hyperglycemia and impaired glucose tolerance in IGF binding protein-1 transgenic mice. Am J Physiol 270(4 Pt 1):E565-71 |
| abstractText | The insulin-like growth factors (IGFs) are present in the serum in association with high-affinity binding proteins (IGFBPs), which limit the hypoglycemic insulin-like actions of these growth factors. By utilizing the mouse phosphoglycerate kinase promoter to drive a rat genomic fragment, we developed three transgenic mouse strains that overexpressed IGFBP-1. Homozygous offspring demonstrated fasting hyperglycemia. The blood glucose values were 4.97 +/- 0.37, 4.57 +/- 0.33, and 5.58 +/- 0.50 mM for transgenic mice compared with 3.33 +/- 0.19 mM (mean +/- SE, P < 0.05) for the wild-type mice. The transgenic mice had more marked hyperglycemia after an intraperitoneal glucose challenge. The fasting serum insulin levels were significantly elevated in the transgenic mice; however, the insulin-to-glucose ratio was only modestly elevated in the fasting state and fell after a glucose challenge. Islet size and number were significantly increased; however, pancreatic insulin content was reduced (P < 0.05) compared with that of wild-type mice. The glucose response to subcutaneous insulin was similar in transgenic and wild-type mice. These data demonstrate that constitutive overexpression of IGFBP-1 results in impaired glucose tolerance with normal insulin sensitivity. |
