Influence of verapamil on glucose tolerance

Verapamil has previously been found to inhibit insulin release from pancreatic beta-cells in laboratory animals. In our department, however, both oral pretreatment with verapamil for one week and a 3-hour iv infusion of the drug improved the tolerance to oral glucose in type II diabetics without affecting insulin release. It failed, however, to potentiate the hypoglycaemic effect of oral glibenclamide therapy in patients with type II diabetes. Since iv infusion of verapamil left the portal vein glucose response to glucose ingestion unaffected in normoglycaemic patients (being portal vein catheterised for diagnostic purposes), it seems unlikely that the hypoglycaemic effect of verapamil could have been due to reduced glucose absorption from the gut. More likely is that verapamil, in the diabetic patients, influenced metabolic processes inside the hepatocytes that are of importance for glucose homeostasis. In-vitro experiments have shown that calcium affects factors of importance for the glucose metabolism. Accordingly, calcium triggers the stimulus-secretion coupling process which leads to insulin release from the pancreatic beta-cells (1). Calcium also tightens cell membranes, thereby decreasing their permeability to various substances, including glucose (2). Finally, calcium mediates cellular responses to glucagon stimulation (3,4) and thus affects the hepatic glucose output. Calcium apparently influences glucose metabolism by several pathways and different overall effects on the blood glucose concentration may be forthcoming depending on which of these pathways is the dominating one.(ABSTRACT TRUNCATED AT 250 WORDS)