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

Abstract

Swiss-Hauschka mice have been selected for high (HG) and low (LG) fasting blood glucose (FBG) levels for four generations. All rantings were brother to sister. Differences in mean FBG levels have remained relatively constant (20 to 30 rag~ 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 Fs, but no further decline was noted in the Fa generation. Fasting serum immunoreactivo insulin (It~I) levels were variable and mean levels for the two lines did not differ significantly. A comparison of glucose tolerance data between F 3 }IG 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. Several in vitro tissue studies revealed no signi~cant 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-6-1~C oxidation rates in ttG line mice may be enhanced.

Genetic Analysis of Glucose Tolerance in Inbred Mouse Strains: Evidence for Polygenic Control

“…This high mutation rate may explain the observation that multiple loci determine the difference in glucose tolerance in the inbred mouse strains examined. On the other hand, Gleason et al (22) observed multiple alleles for glucose tolerance within one inbred strain, suggesting that most of the genetic differences between inbred strains are preexistent in a wild population, with alternative alleles fixed by inbreeding.…”

“…Given this background of complexity for human diabetes, investigators have used inbred mouse strains for genetic analysis (18)(19)(20)(21)(22)(23)(24)(25)(26). An inbred mouse strain represents an almost limitless resource of genetically identical individuals that are predominantly homozygous at every locus (27).…”