The Diabetogenic Effects of Acute Verapamil Poisoning

Abstract

Verapamil poisoning is known to produce hyperglycemia and metabolic acidosis in humans. The purpose of this study was to elucidate mechanisms of verapamil-induced hyperglycemia in awake dogs. Mongrel canines were chronically instrumented to permit studies in the conscious state. In six healthy dogs, steady-state glucose infusion requirement after 1 hr of insulin infusion at 1000 mU/min was 19 ± 1 mg/kg/min. In six separate dogs, verapamil toxicity was induced via verapamil infusion in the portal vein; during verapamil toxicity, the glucose infusion requirement with an insulin infusion rate of 1000 mU/min was significantly decreased (3 ± 1 mg/kg/min;p< 0.05, unpairedttest). Eleven other verapamil-toxic dogs were also treated with either saline (n= 6, 3.0 ml/kg/hr) or glucagon (n= 5, 10 μg/kg/min). Insulin concentrations were not changed vs basal concentrations in either group. Catecholamine concentrations increased at least 15-fold in all groups (from 458 ± 169 to 6973 ± 480 pg/L in the saline-treated group). Glucose concentrations increased in saline-treated animals from 3.7 ± 0.3 to 11.2 ± 1.0 μmol/L, and with glucagon treatment, increased from 3.3 ± 0.3 to 16.1 ± 1.6 μmol/L (p< 0.05 vs saline, ANOVA). Verapamil poisoning appears to produce hyperglycemia by inducing systemic insulin resistance, blocking insulin release, together with an intact stress hormone response and glucogenic capacity.