Abstract
Objective: There are evidences indicating transdermal nitroglycerin changes the sensitivity of peripheral tissues to the hypoglycemic effect of insulin. In this study we determined effect of continuous application of transdermal nitroglycerin patches in healthy volunteers on development of tolerance to the hypotensive effect of nitroglycerin and hypoglycemic effect of insulin. Materials and methods: The effect of transdermal application of nitroglycerin, as NO donor was studied during 24 hours on blood insulin and glucose level and on blood pressure in healthy, young volunteers. Patches of 0.2 mg/ hour nitroglycerine were administered to young healthy volunteers along 24 hours and Venous blood samples were taken early before and 24 hours after the nitroglycerin. Serum was separated and free zed (-80°C) for insulin and glucose determination. Blood pressure also was determined in 6 hours intervals. Results: Before nitroglycerin patches application mean serum insulin level determined level 9.53 ± 4.37 and after nitroglycerin were 9.18 ± μU/ml which is statistically significant (P>0.05). Fasting blood glucose levels were increased by 6.63 ± 1.9 mg/dl determined 24 hours after nitroglycerine application in comparison with before treatment. The changes observed in blood glucose levels also were statistically significant (P<0.001). Insulin resistance calculated by Homa formula was 1.445 before treatment and 1.540 after nitroglycerin treatment. Conclusion: Transdermal nitroglycerin by doses of 0.2 mg/h causing blood glucose level changes more than change of insulin level indicating change in tissue sensitivity to insulin. The present work was therefore concerned with the possibility that nitrate tolerance impairs the sensitivity of tissues to the hypoglycemic effect of insulin.
Highlights
Nitrates producing their effect by releasing nitric oxide (NO) and this substance playing important roles in different organ systems [1]
In the basis of changes observed in serum insulin and blood glucose levels, homeostasis model assessment (Homa) index was determined about 1.445 and 1.540 respectively for before and after nitroglycerine patch administration
This study performed on nondiabetic healthy volunteers without a previous history of other diseases, and our HOMA index calculated were less than 2.5 ruling out the presence of insulin resistance before and after nitroglycerine patch application (12)
Summary
Nitrates producing their effect by releasing nitric oxide (NO) and this substance playing important roles in different organ systems [1]. Nitric oxide have regulatory effects on insulin and carbohydrate metabolism [2,3]. There are many reports about role of nitric oxide on insulin resistance, hypertension, and obesity. In this regards some reports indicating pharmacological inhibition of nitric oxide synthesis increased insulin resistance in human subjects [5]. Marcus et al studies showed a straight relationship between plasma levels of asymmetric dimethylarginine (AMDA) an endogenous inhibitor of nitric oxide synthesis and insulin resistance in healthy human subjects. In Marcus et al study rosiglytazone application was accompanied with enhancement in insulin sensitivity and decrease in plasma AMDA level [6]
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