THE DIABETOGENIC EFFECTS OF ACUTE VERAPAMIL POISONING

Verapamil poisoning is known to produce hyperglycemia and metabolic ac idosis in humans. The purpose of this study was to elucidate mechanism s of verapamil-induced hyperglycemia in awake dogs. Mongrel canines we re 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 i n the portal vein; during verapamil toxicity, the glucose infusion req uirement with an insulin infusion rate of 1000 mU/min was significantl y decreased (3 +/- 1 mg/kg/min; p < 0.05, unpaired t test). Eleven oth er verapamil-toxic dogs were also treated with either saline (n = 6, 3 .0 ml/kg/hr) or glucagon (n = 5, 10 mu g/kg/min). Insulin concentratio ns were not changed vs basal concentrations in either group. Catechola mine concentrations increased at least 15-fold in all groups (from 458 +/- 169 to 6973 +/- 480 pg/L in the saline-treated group). Glucose co ncentrations increased in saline-treated animals from 3.7 +/- 0.3 to 1 1.2 +/- 1.0 mu mol/L, and with glucagon treatment, increased from 3.3 +/- 0.3 to 16.1 +/- 1.6 mu mol/L (p < 0.05 vs saline, ANOVA). Verapami l poisoning appears to produce hyperglycemia by inducing systemic insu lin resistance, blocking insulin release, together with an intact stre ss hormone response and glucogenic capacity, (C) 1997 Academic Press.