title: Hyperinsulinemia but no diabetes in transgenic mice homozygously expressing the tyrosine kinase-deficient human insulin receptor.
abstract: We generated transgenic mice homozygous for the tyrosine kinase-deficient human insulin receptor (hIRK1030M(+/+)) under control of the insulin receptor promoter. Similar growth patterns and results of glucose tolerance tests were observed among normal, heterozygous, and homozygous mice. Insulin tolerance test indicated no significant difference in the hypoglycemic response to insulin among the three genotypes. However, 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) were significantly higher than in the control mice (100.92 +/- 19.55 pg/ml to 356.36 +/- 55.08 pg/ml; p < 0.01 and p < 0.01, respectively) and heterozygous mice (74.46 +/- 18.55 pg/ml to 352.33 +/- 52.43 pg/ml; p < 0.005 and p < 0.01, respectively). Immunohistological evidence of pancreatic islets showed no significant difference among the three genotypes. Taken together, these results suggest that the tyrosine kinase-deficient insulin receptor causes hyperinsulinemia but not diabetes in these homozygous transgenic mice.
authors.affiliation: Division of Molecular Genetics, University of Tokushima, Japan.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Muromoto
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Mitani
authors.forename: H
authors.initials: H
authors.lastname: Uehara
authors.forename: K
authors.initials: K
authors.lastname: Izumi
authors.forename: Y
authors.initials: Y
authors.lastname: Ebina
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D005838:Genotype; D005951:Glucose Tolerance Test; D006720:Homozygote; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics* / Q000503:physiopathology; D007328:Insulin / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D017354:Point Mutation; D011972:Receptor, Insulin / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011972:Receptor, Insulin