title: Genetic analysis of glucose tolerance in inbred mouse strains. Evidence for polygenic control.
abstract: To determine genetic factors involved in diabetes susceptibility in inbred strains of mice, we initially evaluated differences in fed plasma glucose and insulin concentrations among six strains (AKR/J, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, and SWR/J). There was considerable variation in fed plasma glucose concentration, with C3H/HeJ mice the most glucose tolerant (174 +/- 7 mg/dl) and C57BL/6J mice the least glucose tolerant (252 +/- 7 mg/dl, P less than .0001 vs. C3H/HeJ mice). Glycosylated hemoglobin of C57BL/6J mice (4.0 +/- 0.06%) was also higher than that of C3H/HeJ mice (3.52 +/- 0.06%, P less than .0001). The fed plasma insulin concentration did not differ between these two strains. Glucose tolerance was further evaluated in overnight-fasted C3H/HeJ and C57BL/6J mice by an intraperitoneal glucose tolerance test (IPGTT). Although fasting plasma glucose did not differ, the most remarkable difference in plasma glucose during IPGTT between C57BL/6J and C3H/HeJ mice was noted at 30 min (489 +/- 29 vs. 227 +/- 20 mg/dl, P less than .001). To determine the number of genes involved in the phenotypic difference in glucose tolerance, C57BL/6J males were crossed with C3H/HeJ females (F1, C3H/HeJ X C57BL/6J), and the F1 hybrid females were backcrossed with C57BL/6J males (backcrossed, F1 X C57BL/6J). Plasma glucose after 30 min on IPGTT was 219 +/- 8 (n = 21), 456 +/- 18 (n = 23), and 292 +/- 13 (n = 23) mg/dl for C3H/HeJ, C57BL/6J, and F1 mice, respectively (P less than .001 for all comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Metabolism Division, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: K
authors.initials: K
authors.lastname: Kaku
authors.forename: F T
authors.initials: FT
authors.lastname: Fiedorek
authors.forename: M
authors.initials: M
authors.lastname: Province
authors.forename: M A
authors.initials: MA
authors.lastname: Permutt
mesh_terms: D000375:Aging / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics*; D004198:Disease Susceptibility; D005951:Glucose Tolerance Test / Q000662:veterinary*; D006442:Glycated Hemoglobin / Q000378:metabolism; D007328:Insulin / Q000097:blood; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics; D008815:Mice, Inbred Strains / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D013045:Species Specificity
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin