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|Type:||Artigo de periódico|
|Title:||Pancreatic Alpha-Cell Dysfunction Contributes to the Disruption of Glucose Homeostasis and Compensatory Insulin Hypersecretion in Glucocorticoid-Treated Rats|
|Abstract:||Glucocorticoid (GC)-based therapies can cause insulin resistance (IR), glucose intolerance, hyperglycemia and, occasionally, overt diabetes. Understanding the mechanisms behind these metabolic disorders could improve the management of glucose homeostasis in patients undergoing GC treatment. For this purpose, adult rats were treated with a daily injection of dexamethasone (1 mg/kg b.w., i.p.) (DEX) or saline as a control for 5 consecutive days. The DEX rats developed IR, augmented glycemia, hyperinsulinemia and hyperglucagonemia. Treatment of the DEX rats with a glucagon receptor antagonist normalized their blood glucose level. The characteristic inhibitory effect of glucose on glucagon secretion was impaired in the islets of the DEX rats, while no direct effects were found on alpha-cells in islets that were incubated with DEX in vitro. A higher proportion of docked secretory granules was found in the DEX alpha-cells as well as a trend towards increased alpha-cell mass. Additionally, insulin secretion in the presence of glucagon was augmented in the islets of the DEX rats, which was most likely due to their higher glucagon receptor content. We also found that the enzyme 11 beta HSD-1, which participates in GC metabolism, contributed to the insulin hypersecretion in the DEX rats under basal glucose conditions. Altogether, we showed that GC treatment induces hyperglucagonemia, which contributes to an imbalance in glucose homeostasis and compensatory beta-cell hypersecretion. This hyperglucagonemia may result from altered alpha-cell function and, likely, alpha-cell mass. Additionally, blockage of the glucagon receptor seems to be effective in preventing the elevation in blood glucose levels induced by GC administration.|
|Editor:||Public Library Science|
|Citation:||Plos One. Public Library Science, v. 9, n. 4, 2014.|
|Appears in Collections:||Unicamp - Artigos e Outros Documentos|
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