DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20163252

Study of influence of nicorandil on hypoglycemic action of glibenclamide in alloxan induced diabetic rats

Syed Mohsin Ahmed

Abstract


Background: To assess the interaction between ATP - sensitive potassium channel opener nicorandil and potassium channel blocker glibenclamide in alloxan - induced diabetic rats and to evaluate whether nicorandil antagonizes the oral hypoglycaemic action of glibenclamide.

Methods: Insulin secretion involves ATP sensitive K+ channel blockade, the influence of ATP sensitive K+ channel opener was studied in combination with its blocker. Albino rats of wistar strain, weighing between 200 - 250 grams of either sex were used for the study. Diabetes was induced by injecting alloxan monohydrate 2% solution intra - peritoneally in a dose of 150 mg/kg body weight. Animals with fasting blood glucose between 200 - 300 mg/dl were selected and were divided into 3 groups of six animals each. Group I received 2% gum acacia, group II was given glibenclamide (0.5 mg/kg body weight) and group III was treated with nicorandil (0.3 mg/kg body weight) + glibenclamide (0.5 mg/kg body weight) respectively orally for 30 days. Fasting blood sugar was recorded in all rats on 1st, 3rd, 7th, 14th, 21st and 28th days.

Results: Results show that glibenclamide has significantly reduced the blood sugar levels (P<0.05), whereas when glibenclamide was combined with nicorandil there was a significant rise in blood sugar level (P<0.05).

Conclusions: The study shows that hypoglycaemic action of glibenclamide is antagonized by nicorandil as indicated by worsening of diabetes, probably by blocking the K+ channel closing action of glibenclamide. These findings suggest that K+ channel openers should be avoided with K+ channel blockers in presence of diabetes.


Keywords


Diabetes mellitus, Albino rats, Alloxan monohydrate, Fasting blood sugar, Glibenclamide, Nicorandil

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References


Kerins DM, Robertson RM, Robertson D. Drugs used for the treatment of myocardial ischemia. In: Hardman JG, Limbird LE, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill; 2001:1679-80.

Lablanche JM, Bauters C, McFadden FP, Quandalle P, Bertrand ME. Potassium channel activators in vasospastic angina. Eur Heart J. 1993;14(supplement B):22-4.

Oates JA, Brown NJ. Antihypertensive agents and drug therapy of hypertension. In: Hardman JG, Limbird LE, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill; 2001:890-891.

Dunn JS, Sheehan HL, Mcletchie NGB. Necrosis of islets of langerhans produced experimentally. The Lancet. 1943;1(6242):484-7.

Watkins D, Cooperstein SJ, Lazarow A. Effect of alloxan on permeability of pancreatic islet tissue in vitro. Am J Physiol. 1964;207:436-40.

Bailey CC. Alloxan diabetes. Vit Horm. 1949;7;365-82.

Kelestimur F, Kokker H. Alloxan induced diabetes mellitus in albino rats. Ind J Pharmacol. 1994;47:72-5.

Bell RH, Hye RJ. Animal models of diabetes mellitus: physiology and pathology. J Surg Res. 1983;35(5):433-60.

Lekenn FDW. Alloxan diabetes. Pharmacological reviews. 1948;28:304.

Secich P, Wicks F, Lori T. In: Sigma Chemical company, eds. Biochemical organic compounds for research and diagnostic clinical reagents. USA;1995:78.

Windholz M, Merck and Co. The Merck index. 10th ed. Rahway, NJ; 1983:260.

Kennedy MSN, Masharani U. Pancreatic hormones and antidiabetic drugs. In: Katzung BG, Trevor AJ, eds. Basic and Clinical Pharmacology. 9th ed. New York, NY: McGraw-Hill; 2004:705.

Altan. Experimental model of diabetes. Pharmacological reviews. 1989;40:72-5.