Increased calcium-channel currents of pancreatic beta cells in neonatally streptozocin-induced diabetic rats.

Using a whole-cell patch-clamp technique, voltage-dependent Ca(2+)-channel activities were found to be increased in cultured single beta cells isolated from neonatally streptozocin-induced diabetic rats (NSZ rats). The current-voltage relationship and inactivation time course of Ba2+ currents via L-type Ca2+ channels were indistinguishable between NSZ and control rats. However, the current density observed in NSZ rats was significantly greater than that in control rats. Ba2+ currents via T-type Ca2+ channels were also found to be enhanced in NSZ beta cells. The insulin-secretory capacity of cultured pancreatic islets in response to a depolarizing stimulus (20 mmol/L arginine or 30 mmol/L KCl) in the presence of 11.1 mmol/L glucose was augmented in NSZ rats, whereas that in response to 11.1 and 16.7 mmol/L glucose alone was significantly reduced. It is concluded that the impaired insulinotropic action of glucose in beta cells in NSZ rats is not due to reduced activity of voltage-dependent Ca2+ channels. The fact that insulin secretion induced by a depolarizing stimulus was enhanced in NSZ rats may be related to the augmented activity of the voltage-dependent calcium current found in NSZ beta cells.