Genetic selection for high and low fasting blood glucose levels in mice. I. Fasting blood glucose levels,glucose tolerance and isolated tissue studies

Summary Swiss-Hauschka mice have been selected for high (HG) and low (LG) fasting blood glucose (FBG) levels for four generations. All matings were brother to sister. Differences in mean FBG levels have remained relatively constant (20 to 30 mg%) between the two lines since initiation of selection (p<0.001). Body weights have declined more rapidly with inbreeding in the LG line as compared to the HG line through F₃, but no further decline was noted in the F₄ generation. Fasting serum immunoreactive insulin (IRI) levels were variable and mean levels for the two lines did not differ significantly. A comparison of glucose tolerance data between F₃ HG and LG line animals showed generally higher mean glucose levels in the HG line in both fasted and randomfed states. The mean delta glucose levels during the test, however, were nearly identical in both lines. A dietary influence on glucose tolerance was shown. Severalin vitro tissue studies revealed no significant differences in hepatic glycogen and pancreatic insulin content between HG and LG line animals. Isolated tissue sensitivity to insulin appeared indistinguishable between the lines; however, hepatic gluconeogenesis and retinal glucose-6-¹⁴C oxidation rates in HG line mice may be enhanced.Supported in part by U.S.P.H.S. Grants AM-11959, AM-09748, 1-FO3-AM-30777, and AM-05077, and the Upjohn Company, Kalamazoo, Michigan.