The diabetogenic effects of acute verapamil poisoning.
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, unpaired t test). Eleven other verapamil-toxic dogs were also treated with either saline (n = 6, 3.0 ml/kg/hr) or glucagon (n = 5, 10 microg/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 micromol/L, and with glucagon treatment, increased from 3.3 +/- 0.3 to 16.1 +/- 1.6 micromol/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.
Kline
J A
JA
Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina 28232, USA.
Raymond
R M
RM
Schroeder
J D
JD
Watts
J A
JA
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D004285:Dogs; D005260:Female; D005934:Glucagon / Q000627:therapeutic use; D005947:Glucose / Q000627:therapeutic use; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D007262:Infusions, Intravenous; D007328:Insulin / Q000627:therapeutic use; D007329:Insulin Antagonists / Q000633:toxicity; D008297:Male; D012965:Sodium Chloride / Q000627:therapeutic use; D014700:Verapamil / Q000633:toxicity*
D007328:Insulin; D007329:Insulin Antagonists; D012965:Sodium Chloride; D005934:Glucagon; D014700:Verapamil; D005947:Glucose