Effects of diazoxide on α- and β-cell function in isolated perfused rat pancreas

To elucidate the effects of diazoxide on insulin and glucagon secretion at normal, high and low glucose concentrations and 10 mmol/l arginine, we performed pancreatic perfusion experiments. The insulin secretion rate in response to 16.7 mmol/l glucose was dose-dependently suppressed by concomitant infusion of diazoxide (100 and 300 μmol/l). Both the first and second phases of glucose-stimulated insulin secretion were significantly reduced in the presence of diazoxide as compared with controls. Basal glucagon secretion rate at 5.6 mmol/l glucose was significantly reduced by the administration of both 100 and 300 μmol/l diazoxide. Furthermore, the glucagon secretion rate at a high glucose concentration (16.7 mmol/l) was significantly lower with 300 μmol/l diazoxide than in the control. The glucagon secretion rate with glucopenia (1.4 mmol/l) was also significantly lower with 100 and 300 μmol/l diazoxide than in the control. The insulin secretion rate in response to 10 mmol/l arginine was also dose-dependently suppressed by concomitant infusion of diazoxide. The glucagon secretion rate in response to 10 mmol/l arginine was, however, significantly higher with 100 μmol/l diazoxide while not being significantly different with 300 μmol/l diazoxide. These findings suggest that some mechanism(s) which can be inhibited by diazoxide is involved in glucagon, as well as insulin, secretion in isolated perfused rat pancreas.