Nerve Growth Factor Increases Insulin Secretion and Barium Current in Pancreatic β-Cells

• Published in: Diabetes (New York, N.Y.) Vol. 50; no. 8; pp. 1755 - 1762
• Main Authors: ROSENBAUM, T, SANCHEZ-SOTO, M. C, HIRIART, M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2001
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Barium; Barium - metabolism; Biological and medical sciences; Cells, Cultured; Diabetes; Endocrine pancreas; Fundamental and applied biological sciences. Psychology; Glucose; Glucose - pharmacology; Growth factors; Hormones. Régulation; Insulin; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Islets of Langerhans - physiology; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Nerve Growth Factor - immunology; Nerve Growth Factor - pharmacology; Nerve Growth Factor - physiology; Nifedipine - pharmacology; Patch-Clamp Techniques; Physiological aspects; Rats; Rats, Wistar; Vertebrates: endocrinology; Mexico; Pancreatic hormone; Barium; Rat; Langerhans islet; Rodentia; Nerve growth factor; Ionic channel; Insulin; Endocrine secretion; Vertebrata; Mammalia; β Cell; Endocrine pancreas
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.50.8.1755

Nerve Growth Factor Increases Insulin Secretion and Barium Current in Pancreatic β-Cells T. Rosenbaum , M.C. Sánchez-Soto and M. Hiriart Department of Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior, Ciudad Universitaria, Mexico City, Mexico Abstract We analyzed the effect of a brief exposure to nerve growth factor (NGF) on insulin secretion and macroscopic barium currents of single adult rat pancreatic β-cells. After a 1-h exposure to NGF (50 ng/ml), single β-cells show a 2.5-fold increase in the insulin secretion index in 5.6 mmol/l glucose and a nearly twofold increase in 15.6 mmol/l glucose compared with control cells. We have recently demonstrated that pancreatic β-cells synthesize and secrete NGF. We analyzed the effect of endogenous NGF on insulin secretion by incubating islet cells in the presence of an anti-NGF monoclonal antibody for 1 h in different glucose concentrations. Although the basal insulin secretion index (5.6 mmol/l glucose) is not affected, glucose-stimulated insulin secretion (15.6 mmol/l glucose) is decreased by 41% in the presence of the antibody. This effect is mediated by the activation of the NGF receptor TrkA because the specific inhibitor of Trk phosphorylation K252a also blocks NGF-induced increase in insulin secretion, both in the presence and absence of exogenous NGF. Using the whole-cell variation of the patch-clamp technique, we found that cells exposed to NGF for 5 min exhibit a 32% increase in the average barium current density. These results suggest that the effects of NGF on insulin secretion are partially mediated by an increase in calcium current through Ca channels. These results further suggest that NGF plays an important autoregulatory role in pancreatic β-cell function. Two targets of short-term NGF-modulation are insulin secretion and calcium-channel activity. Footnotes Address correspondence and reprint requests to Dr. Marcia Hiriart, Instituto de Fisiología Celular, Department of Biophysics, Ciudad Universitaria, A.P. 70-253 Coyoacán, México D.F. 04510, México. E-mail: mhiriart{at}ifisiol.unam.mx . Received for publication 26 June 2000 and accepted in revised form 10 April 2001. IBa, barium current; LP, large placque-forming; NGF, nerve growth factor; RHPA, reverse hemolytic plaque assay; SP, small placque-forming.