Basic-liver, pancreas, and biliary tractHepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance☆
Section snippets
Transgenic mice
The production of HCV core gene transgenic mice has been described previously.11 Briefly, the core gene from HCV of genotype 1b, which is placed downstream of a transcriptional regulatory region from the hepatitis B virus, was introduced into C57BL/6 mouse embryos (Clea Japan, Tokyo, Japan). The mice were cared for according to institutional guidelines, fed an ordinary chow diet (Funabashi Farms, Funabashi, Japan), and maintained in a specific pathogen-free state. At an indicated time, the mice
Hyperinsulinemia and insulin resistance in transgenic mice
At the age between 1 and 12 months, there was no significant difference in body weight between the core gene transgenic mice and control mice. Figure 1A shows body weight of 2-month-old mice. Fasting plasma glucose (FPG) levels were slightly elevated in the core gene transgenic mice compared with control mice, but the difference was not significant (P = 0.79, Figure 1B). In contrast, there was a marked increase in the level of serum insulin in the core gene transgenic mice than control mice (P
Discussion
Since Allison et al.4 reported an association between HCV infection and diabetes, evidence has been accumulating connecting these 2 conditions. In such studies, HCV infection has a significantly stronger association with diabetes than hepatitis B viral infection.4, 5, 6, 7 The variables other than HCV infection that are associated with diabetes are cirrhosis, male sex,5 and aging.6 In addition to these clinic-based, case-control studies, Mehta et al.7 have reported the result of investigation
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Supported by a grant-in-aid for Scientific Research on Priority Area from the Ministry of Education, Science, Sports and Culture of Japan; Health Sciences Research Grants of The Ministry of Health, Welfare and Labor; The Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Drug ADR Relief, R&D Promotion and Product Review of Japan; and grant from The Sankyo Foundation of Life Science.
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Y.S. and H.F. contributed equally to this work.