Nerve growth factor increases in pancreatic beta cells after streptozotocin-induced damage in rats.
We investigated short-term in vivo and in vitro effects of streptozotocin (STZ) on pancreatic beta cells. Male Wistar rats were treated with 75 mg/kg STZ, and, after 4 hrs blood glucose and insulin were measured and islet cells were isolated, cultured for 16 hrs, and challenged with 5.6 and 15.6 mM glucose. Treated rats showed hyperglycemia (approximately 14 mM) and a 70% decrease in serum insulin levels as compared with controls. Although insulin secretion by isolated beta cells from STZ-treated rats was reduced by more than 80%, in both glucose concentrations, nerve growth factor (NGF) secretion by the same cells increased 10-fold. Moreover, NGF messenger RNA (mRNA) expression increased by 30% as compared with controls. Similar results were obtained in an in vitro model of islet cells, in which cells were exposed directly to STZ for 1, 2, and 4 hrs and then challenged for 3 hrs with the same glucose concentrations. Our data strongly suggest that an early increase in NGF production and secretion by beta cells could be an endogenous protective response to maintain cell survival and that diabetes mellitus may occur when this mechanism is surpassed.
Larrieta
Maria Elena
ME
Department of Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autonoma de México, UNAM, Ciudad Universitaria, D. F. 04510, México.
Vital
Paz
P
Mendoza-Rodríguez
Adriana
A
Cerbón
Marco
M
Hiriart
Marcia
M
D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000097:blood / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D013311:Streptozocin; D020932:Nerve Growth Factor