Science

Hepatitis C virus directly involved in insulin resistance

Last Updated: 2004-03-09 11:06:38 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Hepatitis C virus (HCV) is directly involved in the development of insulin resistance, according to a report in the March issue of Gastroenterology.

HCV infection has been associated with type 2 diabetes, the authors explain, but a definite causative relationship between HCV infection and diabetes has not been established.

Dr. Kazuhiko Koike, and colleagues from University of Tokyo, studied the role of HCV in the development of diabetes using transgenic mice that carry the core gene of HCV.

"Hyperinsulinemia was observed in the core gene transgenic mice as early as 1 month old," the authors report. Insulin resistance was observed by the age of 2 months.

Administration of glucose to core gene transgenic mice revealed only mild and statistically insignificant glucose intolerance compared with control mice, the results indicate, but transgenic mice fed a high-fat diet developed overt diabetes.

Insulin resistance depended chiefly on the shortage of insulin action on the liver, the researchers note, whereas skeletal muscle contributed little to the development of insulin resistance.

Suppression of insulin action in the liver resulting from TNF-alpha-mediated suppression of tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) is at least one of the mechanisms of insulin resistance in this model, the investigators report, and TNF-alpha blockade restored insulin sensitivity.

The authors conclude, "The HCV core protein induces insulin resistance in transgenic mice without gain in body weight at young age. These results indicate a direct involvement of HCV per se in the pathogenesis of diabetes in patients with HCV infection and provide a molecular basis for insulin resistance in such a condition."

"The study makes a major contribution by showing that hepatic insulin resistance can be induced solely by expression of the HCV core protein, and that signaling abnormalities in the insulin receptor-IRS-1 pathway are present before the development of steatosis," write Dr. Steven A. Weinman and Dr. L. Maria Belalcazar from University of Texas Medical Branch, Galveston, in a related editorial.

"The article...makes an important contribution to putting the HCV-diabetes association on a mechanistic footing, thus elevating it from a curious association to an important disease process."

Gastroenterology 2004;126:840-848,917-919.