In vitro effects of BAY K 8644, a dihydropyridine derivative with hypoglycaemic properties, on hepatic glucose production and pancreatic hormone secretion.

In rats, oral administration of BAY K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate), a dihydropyridine derivative, Ca2+-channel activator, lowers fasting glycaemia and improves glucose tolerance to carbohydrate loading without elevating peripheral plasma insulin. To study the hypoglycaemic mechanism of this compound, we have examined its effects on glucose production by isolated rat hepatocytes and on hormone secretion by the perfused rat pancreas. Incorporation of BAY K 8644 (0.2-10 microM) into the hepatocyte incubation medium failed to significantly modify glycogenolysis, gluconeogenesis or L-lactate production. Hepatocyte glycogen phosphorylase a (EC 2.4.1.1) activity and fructose 2,6-bisphosphate levels were also unaffected by BAY K 8644. In the perfused rat pancreas, BAY K 8644 markedly stimulated insulin release without modifying glucagon or somatostatin output. Thus, the possibility that this compound exerts its hypoglycaemic effect by provoking insulin secretion should be further investigated.