Abstract
In the present study by Dodig and colleagues, published in Metabolism and Target Organ Damage , the authors investigate the role of insulin in promoting type I collagen synthesis in hepatic stellate cells (HSCs) through α5β1 integrin signaling. Using L-SACC1 transgenic mice, which exhibit hyperinsulinemia and insulin resistance without fasting hyperglycemia, the researchers demonstrate that elevated insulin levels significantly increase type I collagen production in HSCs. This effect is mediated by α5β1 integrin signaling rather than the PI3 kinase pathway. These findings suggest that chronic hyperinsulinemia may preprogram HSCs for enhanced fibrogenesis following liver injury, contributing to advanced fibrosis associated with metabolic disorders such as metabolic dysfunction-associated steatosis liver disease (MASLD) and type 2 diabetes. It further suggests that chronic hyperinsulinemia increases the risk of significant fibrosis burden in chronic liver disease. In this commentary, the strengths and limitations of this study are discussed, along with the potential impact of these findings on current treatment strategies for insulin resistance, endogenous hyperinsulinemia, and exogenous hyperinsulinemia in the development of MASLD and disease progression to fibrosis, cirrhosis, and hepatocellular carcinoma.
Published Version
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