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Experimental Biology and Medicine 231:396-402 (2006)
© 2006 Society for Experimental Biology and Medicine

ORIGINAL RESEARCH ARTICLE

Nerve Growth Factor Increases in Pancreatic ß Cells After Streptozotocin-Induced Damage in Rats

Maria Elena Larrieta*, Paz Vital*, Adriana Mendoza-Rodríguez{dagger}, Marco Cerbón{dagger} and Marcia Hiriart*,1

* Department of Biophysics, Instituto de Fisiología Celular; and {dagger} Department of Biology, Facultad de Química, Universidad Nacional Autonóma de México, UNAM, Circuito Exterior, Ciudad Universitaria, D. F. 04510, Mexico

To whom requests for reprints should be addressed at 1 Department of Biophysics, Instituto de Fisiología Celular, UNAM; Ciudad Universitaria, AP 70-253 Coyoacán, México D. F. 04510, México. E-mail: mhiriart{at}ifc.unam.mx

We investigated short-term in vivo and in vitro effects of streptozotocin (STZ) on pancreatic ß 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 (~14 mM) and a 70% decrease in serum insulin levels as compared with controls. Although insulin secretion by isolated ß 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 ß cells could be an endogenous protective response to maintain cell survival and that diabetes mellitus may occur when this mechanism is surpassed.

Key Words: insulin secretion • diabetes mellitus • ELISA • NGF mRNA • TUNEL






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