Hepatic insulin receptor: new views on the mechanisms of liver disease

Over 65 % of people with obesity display the metabolic-associated fatty liver disease (MAFLD), which can manifest as steatohepatitis, fibrosis, cirrhosis, or liver cancer. The development and progression of MAFLD involve hepatic insulin resistance and reduced insulin clearance. This review discusses the relationships between altered insulin signaling, hepatic insulin resistance, and reduced insulin clearance in the development of MAFLD and how this provides the impetus for exploring the use of insulin sensitizers to curb this disease. The review also explores the role of the insulin receptor in hepatocytes and hepatic stellate cells and how it signals in metabolic and end-stage liver diseases. Finally, we discuss new research findings that indicate that advanced hepatic dis-eases may be an insulin-sensitive state in the liver and deliberate whether insulin sensitizers should be used to manage late-stage liver diseases.

Automated summary

Over 65% of obese individuals suffer from metabolic-associated fatty liver disease (MAFLD), which can lead to various conditions such as steatohepatitis, fibrosis, cirrhosis, or liver cancer. This review discusses the role of insulin signaling, hepatic insulin resistance, and reduced insulin clearance in the development of MAFLD, emphasizing the potential use of insulin sensitizers as a treatment approach. Additionally, the review explores the involvement of the insulin receptor in hepatocytes and hepatic stellate cells and its implications in metabolic and end-stage liver diseases. It also discusses the possibility of using insulin sensitizers to manage late-stage liver diseases based on recent research findings.