LIFELONG ENHANCED DIABETES SUSCEPTIBILITY AND OBESITY AFTER TEMPORARY INTRAHYPOTHALAMIC HYPERINSULINISM DURING BRAIN ORGANIZATION

Newborn male Wistar-rats received bilateral intrahypothalamic insulin-agar-implants on the 2nd or 8th day of life. In male control animals only the insulin-free indifferent agar-vehicle was implanted at the same age. In both experimental groups with temporary intrahypothalamic hyperinsulinism during brain organization the following results were obtained: 1) Higher body weight gain starting at the end of the hypothalamic differentiation period and continuing during juvenile life until adulthood, resulting in increased relative body weight as a sign of obesity; 2) A tendency to basal hyperinsulinaemia in juvenile and adult age; 3) Impaired glucose tolerance in adulthood; 4) Increased diabetes susceptibility to a single "subdiabetogenic" dose of streptozotocin in adult age. In view of these and previous observations a teratogenetic role of high insulin concentrations during the organization of glucoregulatory hypothalamic structures is hypothesized and the possible relevance of such hyperinsulinism as a predisposing factor for a lifelong enhanced diabetes and/or obesity risk is suggested.