Influence of Verapamil on Glucose Tolerance

Abstract

Summary Verapamil has previously been found to inhibit insulin release from pancreatic β‐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 hypoglyemic 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 hypoglyceamic 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 β‐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. In view of these well‐documented in‐vitro effects of calcium on some of the metabolic processes which determine the glucose tolerance, it is surprising to find that relatively few clinical studies have been carried out to investigate whether calcium antagonists influence glucose tolerance in man. Although a few such studies, dealing with the effect of nifedipine (5,6) and verapamil (7,8,9,10) on human glucose tolerance have been performed recently, the result obtained in these investigations have been highly conflicting. Our intention has therefore been to elucidate how oral and iv administration of verapamil affects glucose tolerance not only in normoglycaemic subjects, but also in patients with untreated, and sulfonylurea‐treated type II diabetes.