Hyperinsulinemia caused by dexamethasone treatment is associated with reduced insulin clearance and lower hepatic activity of insulin-degrading enzyme.

Abstract

OBJECTIVES:

Glucocorticoid treatment induces insulin resistance (IR), which is counteracted by a compensatory hyperinsulinemia, due to increased pancreatic β-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 [1mg/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.

• Authors: André Otávio Peres Protzek, Luiz Fernando Rezende, José Maria Costa-Júnior, Sandra Mara Ferreira, Ana Paula Gameiro Cappelli, Flávia Maria Moura de Paula, Jane Cristina de Souza, Mirian Ayumi Kurauti, Everardo Magalhães Carneiro, Alex Rafacho, Antonio Carlos Boschero
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 155 Issue Pt A Pg. 1-8 (Jan 2016) ISSN: 1879-1220 [Electronic] England
• PMID: 26386462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Glucocorticoids
• Insulin
• Dexamethasone
• Insulysin

Topics

• Animals
• Dexamethasone (adverse effects, pharmacology)
• Glucocorticoids (adverse effects, pharmacology)
• Glucose Tolerance Test
• Hyperinsulinism (chemically induced, metabolism)
• Insulin (metabolism)
• Insulin Resistance
• Insulysin (genetics, metabolism)
• Liver (drug effects, metabolism)
• Male
• Mice
• Rats, Wistar