Inheritance of Diabetes Mellitus as Consequence of Gestational Hyperglycemia in Rats

  1. Luc Picon
  1. Laboratory of Developmental Physiology, University of Paris Paris, France
  1. Address correspondence and reprint requests to A. Ktorza, Laboratoire de Physiologie du Développement, Université Paris 7, Centre National de la Recherche Scientifique, URA 307, T 23–33, 1er Étage, 2 Place Jussieu, 75251 Paris Cedex 05, France.

Abstract

Our study investigated whether a deterioration of glucose homeostasis and insulin secretion in adult female rats from hyperglycemic dams could be transmitted to the next generation independent of genetic interferences. Dams (F0) were rendered hyperglycemic by continuous glucose infusion during the last week of pregnancy. Females born of these rats (F1) exhibited glucose intolerance and impaired insulin secretion in vivo at adulthood. When they were 3 mo old, they were mated with males born of control dams. During pregnancy, their glucose tolerance remained impaired compared with that of controls. Consequently, F2 newborns of F1 hyperglycemic dams showed the main features of newborns from diabetic mothers: they were hyperglycemie, hyperinsulinemic, and macrosomic. As adults, they displayed basal hyperglycemia and defective glucose tolerance and insulin secretion. This indicates that the long-range deteriorating effects on glucose homeostasis of gestationai hyperglycemia in the F1generation are transmitted to the F2 generation and suggests that a perturbed fetal metabolic environment contributes to the inheritance of diabetes mellitus.

  • Received April 20, 1989.
  • Revision received December 28, 1989.
  • Accepted December 28, 1989.
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