HIGHER MATERNAL THAN PATERNAL INHERITANCE OF DIABETES IN GK RATS

Results from crosses between Goto-Kakizaki (GK) rats, which exhibit sp ontaneous non-insulin-dependent diabetes mellitus (NIDDM), and outbred nondiabetic Wistar rats have demonstrated an effect of maternal inher itance on diabetes in offspring of the first generation (F1). At 6 wee ks of age, F1 offspring of sex-directed crosses exhibited plasma gluco se values intermediate between GK and Wistar parents. Hyperglycemia in F1 rats born of female GK rats (F1GK) was more marked than in those b orn of female Wistar (F1W) rats. At 3 months of age, F1 rats showed a marked impairment of both glucose tolerance and insulin secretion, whi ch was intermediate between GK and Wistar rats. Glucose intolerance wa s more pronounced is F1GK rats than in F1W. By contrast, insulin secre tion in F1W rats was more deteriorated than in F1GK rats. No deletion in mitochondrial DNA was observed in the GK rats, which decreased the possibility of a mitochondrial inheritance effect as an explanation of our findings. These data support a polygenic model in diabetes inheri tance of NIDDM and suggest that, in addition to genetic factors, a per turbed maternal metabolism can contribute to its inheritance.