Role of the mineralocorticoid receptor in hypoglycemia-induced inflammation in humans
Hypoglycemia has been implicated in the pathophysiology of cardiovascular disease. Hypoglycemia is also known to increase both inflammatory factors and counterregulatory hormones. Although the mechanism by which hypoglycemia contributes to cardiovascular injury is unclear, it is suspected that elevation of inflammatory factors and counterregulatory hormones are associated with this injury. Several studies have demonstrated a possible role of the mineralocorticoid receptor in hypoglycemia-associated autonomic failure and thus diminished autonomic control of the heart. Furthermore, activation of the mineralocorticoid receptor is pro-inflammatory. Cortisol and aldosterone, both of which are ligands to the mineralocorticoid receptor, are elevated during hypoglycemia. Our aim in conducting this study was to test the hypothesis that blockade of the mineralocorticoid receptor will reduce the pro- inflammatory effects of hypoglycemia-induced inflammation. In a clinical study of 7 healthy men and women, we found that administration of a mineralocorticoid receptor antagonist blunted the elevation of IL-6 during hypoglycemia. Results in this thesis demonstrate that antagonism at the mineralocorticoid receptor may minimize elevation of inflammation via IL-6, and suggest that activity at the mineralocorticoid receptor may be a means to address the effects of hypoglycemia-induced inflammation.
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