Artículos de revistas
Hyperinsulinemia Caused By Dexamethasone Treatment Is Associated With Reduced Insulin Clearance And Lower Hepatic Activity Of Insulin-degrading Enzyme
Registro en:
Hyperinsulinemia Caused By Dexamethasone Treatment Is Associated With Reduced Insulin Clearance And Lower Hepatic Activity Of Insulin-degrading Enzyme. Pergamon-elsevier Science Ltd, v. 155, p. 1-8 JAN-2016.
0960-0760
WOS:000367424000001
10.1016/j.jsbmb.2015.09.020
Autor
Peres Protzek
Andre Otavio; Rezende
Luiz Fernando; Costa-Junior
Jose Maria; Ferreira
Sandra Mara; Gameiro Cappelli
Ana Paula; Moura de Paula
Flavia Maria; de Souza
Jane Cristina; Kurauti
Mirian Ayumi; Carneiro
Everardo Magalhaes; Rafacho
Alex; Boschero
Antonio Carlos
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objectives: Glucocorticoid treatment induces insulin resistance (IR), which is counteracted by a compensatory hyperinsulinemia, due to increased pancreatic beta-cell function. There is evidence for also reduced hepatic insulin clearance, but whether this correlates with altered activity of insulin-degrading enzyme (IDE) in the liver, is not fully understood. Here, we investigated whether hyperinsulinemia, in glucocorticoid-treated rodents, is associated with any alteration in the insulin clearance and activity of the IDE in the liver. Materials/methods: Adult male Swiss mice and Wistar rats were treated with the synthetic glucocorticoid dexamethasone intraperitoneally [1 mg/kg body weight (b.w.)] for 5 consecutive days. Results: Glucocorticoid treatment induced IR and hyperinsulinemia in both species, but was more impactful in rats that also displayed glucose intolerance and hyperglycemia. Insulin clearance was reduced in glucocorticoid-treated rats and mice, as judged by the reduction of insulin decay rate and increased insulin area-under-the-curve (47% and 87%, respectively). These results were associated with reduced activity (35%) of hepatic IDE in rats and a tendency to reduction (p = 0.068) in mice, without alteration in hepatic IDE mRNA content, in both species. Conclusion: In conclusion, the reduced insulin clearance in glucocorticoid-treated rodents was due to the reduction of hepatic IDE activity, at least in rats, which may contributes to the compensatory hyperinsulinemia. These findings corroborate the idea that short-term and/or partial inhibition of IDE activity in the liver could be beneficial for the glycemic control. (C) 2015 Elsevier Ltd. All rights reserved. 155
1 8 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FAPESP [2010-05196-2]