Verapamil Inhibits the Glucose Transport Activity of GLUT1

被引：15

作者：

Louters L.L. ^{[1
]}

Stehouwer N. ^{[1
]}

Rekman J. ^{[1
]}

Tidball A. ^{[1
]}

Cok A. ^{[1
]}

Holstege C.P. ^{[2
]}

机构：

[1] Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI

[2] Division of Medical Toxicology, Department of Emergency Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908-0774

来源：

Journal of Medical Toxicology | 2010年 / 6卷 / 2期

关键词：

Calcium channel blocker; GLUT1; Insulin; Toxicity;

D O I：

10.1007/s13181-010-0072-z

中图分类号：

学科分类号：

摘要：

Calcium channel blocker toxicity has been associated with marked hyperglycemia responsive only to high-dose insulin therapy. The exact mechanism(s) of this induced hyperglycemia has not been clearly delineated. The glucose transporter GLUT1 is expressed in a wide variety of cell types and is largely responsible for a basal level of glucose transport. GLUT1 also is activated by cell stress. The specific purpose of this study was to investigate the effects of the calcium channel blocker verapamil on the glucose uptake activity of GLUT1 in L929 fibroblasts cells. Dose-dependent effects of verapamil on glucose uptake were studied using L929 fibroblast cells with 2-deoxyglucose. Verapamil had a dose-dependent inhibitory effect on both basal and stress-activated transport activity of GLUT1. Basal activity was inhibited 50% by 300 μM verapamil, while 150 μM verapamil completely inhibited the activation induced by the stress of glucose deprivation. These effects were reversible and required verapamil to be present during the stress. Alteration of calcium concentrations by addition of 5 mM CaCl2 or 4 mM EDTA had no effect on verapamil action. This study reveals the unique finding that verapamil has inhibitory effects on the transport activity of GLUT1 independent of its effects on calcium concentrations. The inhibition of GLUT1 may be one of the contributing factors to the hyperglycemia observed in CCB poisoning. © 2010 American College of Medical Toxicology.

引用

页码：100 / 105

页数：5

共 32 条

[1]

Bronstein A.C., Spyker D.A., Cantilena J.L.R., Green J.L., Rumack B.H., Heard S.E., Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report, Clin Toxicol (Phila), 46, 10, pp. 927-1057, (2008)

[2]

Litovitz T.L., Felberg L., White S., Klein-Schwartz W., 1995 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System, Am J Emerg Med, 14, 5, pp. 487-537, (1996)

[3]

Bechtel L.K., Haverstick D.M., Holstege C.P., Verapamil toxicity dysregulates the phosphatidylinositol 3-kinase pathway, Acad Emerg Med, 15, 4, pp. 368-374, (2008)

[4]

Boyer E.W., Duic P.A., Evans A., Hyperinsulinemia/euglycemia therapy for calcium channel blocker poisoning, Pediatr Emerg Care, 18, 1, pp. 36-37, (2002)

[5]

Dewitt C.R., Waksman J.C., Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity, Toxic Rev, 23, 4, pp. 223-238, (2004)

[6]

Holstege C., Kirk M., Furbee R., Wermuth M., Wide complex dysrhythmia in calcium channel blocker overdose responsive to sodium bicarbonate, J Toxicol Clin Toxicol, 36, 5, (1998)

[7]

Ohta M., Nelson J., Nelson D., Meglasson M.D., Erecinska M., Effect of Ca++ channel blockers on energy level and stimulated insulin secretion in isolated rat islets of Langerhans, J Pharmacol Exp Ther, 264, 1, pp. 35-40, (1993)

[8]

Tanen D.A., Ruha A.M., Curry S.C., Graeme K.A., Reagan C.G., Hypertonic sodium bicarbonate is effective in the acute management of verapamil toxicity in a swine model, Ann Emerg Med, 36, 6, pp. 547-553, (2000)

[9]

Tenharmsel A., Holstege C.P., Louters L.L., High dose insulin reverses verapamil inhibition of glucose uptake in mouse striated muscle (abstract), Ann Emerg Med, 46, (2005)

[10]

Kline J.A., Raymond R.M., Schroeder J.D., Watts J.A., The diabetogenic effects of acute verapamil poisoning, Toxicol Appl Pharmacol, 145, 2, pp. 357-362, (1997)

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