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.
Plagemann
A
A
Institute of Experimental Endocrinology, Humboldt University Medical School (Charité), Berlin/Germany.
Heidrich
I
I
Götz
F
F
Rohde
W
W
Dörner
G
G
D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D003920:Diabetes Mellitus / Q000209:etiology* / Q000401:mortality; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005947:Glucose / Q000502:physiology; D006946:Hyperinsulinism / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D008297:Male; D009765:Obesity / Q000209:etiology* / Q000401:mortality; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D004343:Drug Implants; D007328:Insulin; D005947:Glucose