Diabetes, Vol 43, Issue 2 220-224, Copyright © 1994 by American Diabetes Association
Higher maternal than paternal inheritance of diabetes in GK rats
D Gauguier, I Nelson, C Bernard, V Parent, C Marsac, D Cohen and P Froguel
INSERM U75, Paris, France.
Results from crosses between Goto-Kakizaki (GK) rats, which exhibit
spontaneous non-insulin-dependent diabetes mellitus (NIDDM), and outbred
nondiabetic Wistar rats have demonstrated an effect of maternal inheritance
on diabetes in offspring of the first generation (F1). At 6 weeks of age,
F1 offspring of sex-directed crosses exhibited plasma glucose values
intermediate between GK and Wistar parents. Hyperglycemia in F1 rats born
of female GK rats (F1GK) was more marked than in those born of female
Wistar (F1W) rats. At 3 months of age, F1 rats showed a marked impairment
of both glucose tolerance and insulin secretion, which was intermediate
between GK and Wistar rats. Glucose intolerance was more pronounced in F1GK
rats than in F1W. By contrast, insulin secretion 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 inheritance of NIDDM and suggest that, in
addition to genetic factors, a perturbed maternal metabolism can contribute
to its inheritance.