4.6 Review

Insulin Resistance across the Spectrum of Nonalcoholic Fatty Liver Disease

Journal

METABOLITES
Volume 11, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/metabo11030155

Keywords

insulin resistance; NAFLD; cirrhosis; hepatogenous diabetes

Funding

  1. Liver Investigation Testing Marker Utility in Steatohepatitis (LITMUS) project
  2. Innovative Medicines Initiative 2 Joint Undertaking [777377]
  3. European Union's Horizon 2020 research and innovation program
  4. EFPIA
  5. Italian Ministry for Education, University and Research (Ministero dell'Istruzione, dell'Universita e della Ricerca-MIUR) under the program Dipartimenti di Eccellenza 2018-2022 [D15D18000410001]

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Insulin resistance is defined as a lower-than-expected response to insulin action from target tissues, leading to the development of type 2 diabetes, and is also associated with nonalcoholic fatty liver disease and the progression of nonalcoholic steatohepatitis. Major contributors for the development and worsening of insulin resistance include the liver, adipose tissue, and skeletal muscle.
Insulin resistance (IR) is defined as a lower-than-expected response to insulin action from target tissues, leading to the development of type 2 diabetes through the impairment of both glucose and lipid metabolism. IR is a common condition in subjects with nonalcoholic fatty liver disease (NAFLD) and is considered one of the main factors involved in the pathogenesis of nonalcoholic steatohepatitis (NASH) and in the progression of liver disease. The liver, the adipose tissue and the skeletal muscle are major contributors for the development and worsening of IR. In this review, we discuss the sites and mechanisms of insulin action and the IR-related impairment along the spectrum of NAFLD, from simple steatosis to progressive NASH and cirrhosis.

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