Journal
JOURNAL OF HEPATOLOGY
Volume 40, Issue 1, Pages 47-51Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2003.09.020
Keywords
alanine transaminase; steatohepatitis; non-alcoholic steatohepatitis; glucose; insulin resistance; quantitative insulin sensitivity check index; liver
Categories
Funding
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [R01HD040027] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK059580] Funding Source: NIH RePORTER
- NICHD NIH HHS [R01 HD40027] Funding Source: Medline
- NIDDK NIH HHS [R01 DK59580] Funding Source: Medline
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Background Aims: Non-alcoholic steatohepatitis is an important disease whose pathophysiology remains incompletely understood, although in humans a strong association with insulin resistance exists. Mice fed a methionine-choline deficient (MCD) diet develop steatohepatitis, however the influence of insulin in this model is unknown. Methods: Male FVB/NJ mice were fed the MCD, MCD control or chow diet for 10 or 28 days. Fasting glucose, ALT, triglyceride and insulin was measured. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed followed by quantitative insulin sensitivity check index (QUICKI) determination. Results: ALT levels were significantly higher in the MCD group. Fasting glucose was 81 +/- 5 mg/dl in MCD diet fed mice, compared to MCD controls (196 +/- 46 mg/dl) and chow (199 +/- 15 mg/dl) (P < 0.0001). During GTT and ITT, the effect of glucose administration on blood glucose was dampened, and the insulin effect more pronounced in the MCD group (P = 0.026 and P < 0.001). QUICKI in MCD fed mice was significantly higher than in the chow fed mice. Conclusions: GTT, ITT and QUICKI confirmed the absence of insulin resistance in the MCD fed mice. This model causes fibrosing steatohepatitis and may help delineate the non-insulin resistant mechanisms involved in human steatohepatitis. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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