Insulin-Dependent Brain Organization and Diabetes Mellitus

Summary

When adult female rats (first generation) were injected with 30 mg of streptozotocin per kg body weight (b.w.) on the first day of pregnancy they developed a mild gestational diabetes. Their offspring (second as well as third generation) displayed increased plasma insulin levels in neonatal life and hypoplasia of the hypothalamic ventromedial nuclei throughout life as well as altered hypothalamic monoamine and β-endorphin concentrations. In adulthood, the offspring exhibited decreased tolerance and increased susceptibility to streptozotocin diabetes, associated with enhanced spleen cell cytotoxicity against β-cells. Such teratogenetic diabetes susceptibility is only transmitted on the maternal side via gestational diabetes, leading to pre- or early postnatal hyperinsulinism. Thus, hyperinsulinism during brain organization, produced by impaired glucose tolerance in pregnancy, is a predisposing teratogenetic factor for the development of diabetes in the offspring. Our experimental data are in agreement with clinical findings: (1) Diabetes transmission between generations was found to be 2–3 times higher on the maternal side than on the paternal side. (2) Subjects born in periods with high food supply showed a significantly higher diabetes prevalence than those born in periods with shortage of food supply. (3) A significantly decreased prevalence of childhood-onset diabetes could be achieved in Berlin/GDR since 1973 by improving systematically diagnostic and therapeutic measures for gestational diabetics.