Hyperglycemia and impaired glucose tolerance in IGF binding protein-1 transgenic mice

Am J Physiol. 1996 Apr;270(4 Pt 1):E565-71. doi: 10.1152/ajpendo.1996.270.4.E565.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Fasting
  • Glucose / physiology*
  • Glucose Intolerance
  • Hyperglycemia / genetics*
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Insulin / blood
  • Insulin / pharmacology
  • Insulin-Like Growth Factor Binding Protein 1 / genetics*
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Mice
  • Mice, Transgenic
  • Organ Size
  • Pancreas / metabolism
  • Pancreas / pathology
  • RNA, Messenger / metabolism
  • Rats

Substances

  • Blood Glucose
  • Insulin
  • Insulin-Like Growth Factor Binding Protein 1
  • RNA, Messenger
  • Glucose