The role of liver in insulin resistance development
Journal Title: Postępy Nauk Medycznych - Year 2010, Vol 23, Issue 1
Abstract
Reduced insulin sensitivity is considered to be the key pathomechanism of metabolic syndrome. Recently relationship between insulin resistance and liver steatosis has become a focus for research. However, mechanisms of liver insulin resistance still remain to be elucidated. Non-alcoholic fatty liver disease (NAFLD) including both simple steatosis and non-alcoholic steatohepatitis (NASH), which can progress to fibrosis, and subsequently to liver cirrhosis and hepatocellular carcinoma, is now considered to be the hepatic manifestations of metabolic syndrome. Obesity, dyslipidaemia, type 2 diabetes, hypertension and other components of metabolic syndrome actively correlate with development of NAFLD and NASH. Abnormal metabolism and peroxidation of fatty acids, increased lipolysis and increased supply of lipids to liver appear to play a crucial role, resulting in free fatty acid accumulation in hepatocytes and oxidative stress. A candidate underlying mechanism of insulin resistance and NAFLD development is increased cytochrome P450 expression, resulting in excessive release of reactive oxygen species, which participate in inflammatory and fibrosis process of NAFLD. Adipocytokines such as adiponectin, resistin, leptin, TNF-a and IL-6 have been implicated to be associated with insulin resistance in liver. Another mechanism priming insulin resistance is components of renin-angiotensin-system. It is suggested, that NAFLD and the proinflammatory state are key to the development of metabolic syndrome. The article presents potential mechanisms and hypotheses on the development of liver insulin resistance.
Authors and Affiliations
Agnieszka Zwolak, Iwona Jastrzębska, Michał Tomaszewski, Beata Kasztelan-Szczerbińska, Barbara Skrzydło-Radomańska, Jadwiga Daniluk
Keywords
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