Hyperglycemia and impaired glucose tolerance in IGF binding protein-1 transgenic mice.
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.
Rajkumar
K
K
Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
Dheen
S T
ST
Murphy
L J
LJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005215:Fasting; D005947:Glucose / Q000502:physiology*; D018149:Glucose Intolerance; D006943:Hyperglycemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics* / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D005947:Glucose