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Hemodynamic Consequences of Recurrent Insulin ‐ Induced Hypoglycemia

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Clinical and Experimental Pharmacology and Physiology

Published online on

Abstract

1.Recurring insulin‐induced hypoglycemia (RIIH) often occurs during the therapeutic management of insulin dependent diabetes mellitus. Controversy currently exists in the literature as to the ability of insulin and/or hypoglycemia to promote hypertension. Could insulin and/or hypoglycemia promote adverse pressor effects; if so, under what conditions and through what mechanism? Thus, the current study was performed to evaluate the hypothesis that recurrent insulin‐induced hypoglycemia produces hypertension via an induction in HO‐1 promoting a significant increase in endogenous CO. 2.Male Sprague Dawley rats were treated for 2 weeks with varying doses of subcutaneous insulin injections (1, 3, 5, 7, and 9 U/kg body weight) or vehicle and fed normal rat chow or zinc diet (1mM) for 2 weeks. Tail‐cuff blood pressure, food/water intake and blood glucose states were monitored daily. 3.A dose dependent decrease in blood glucose was observed. The blood pressure was significantly elevated in rats treated with 9 U/Kg and 7U/Kg doses as compared to other units. However, there was no change in urine output among all the groups. High zinc diet + 7U/Kg and HO‐1 inhibitor ZnDPBG (20mg/kg) treatments produced a significant reduction in blood pressure as compared to 7U/Kg alone. In addition, HO‐1 protein levels in heart and kidney and endogenous CO levels were reduced in high zinc diet + 7U/Kg vs 7U/Kg rats. 4.These results demonstrate that RIIH promotes hypertension and restoration of normal CO levels with a high zinc diet and ZnDPBG reduces the blood pressure. This article is protected by copyright. All rights reserved.