HYPERINSULINEMIA BUT NO DIABETES IN TRANSGENIC MICE HOMOZYGOUSLY EXPRESSING THE TYROSINE KINASE-DEFICIENT HUMAN INSULIN-RECEPTOR

We generated transgenic mice homozygous for the tyrosine kinase-defici ent human insulin receptor (hIR(K1030M)(+/+)) under control of the ins ulin receptor promoter. Similar growth patterns and results of glucose tolerance tests mere observed among normal, heterozygous, and homozyg ous mice. Insulin tolerance test indicated no significant difference i n the hypoglycemic response to insulin among the three genotypes. Howe ver, the serum insulin levels of the homozygous mice before and after glucose loading (201.42 +/- 58.15 pg/ml to 578.57 +/- 49.03 pg/ml) wer e significantly higher than in the control mice (100.92 +/- 19.55 pg/m l to 356.36 +/- 55.08 pg/ml; p<0.01 and p<0.01, respectively) and hete rozygous mice (74.46 +/- 18.55 pg/ml to 352.33 +/- 52.43 pg/ml; p<0.00 5 and p<0.01, respectively). Immunohistological evidence of pancreatic islets showed no significant difference among the three genotypes. Ta ken together, these results suggest that the tyrosine kinase-deficient insulin receptor causes hyperinsulinemia but not diabetes in these ho mozygous transgenic mice. (C) 1997 Academic Press.