Hepatic insulin resistance

Hepatic insulin resistance refers to the reduced responsiveness of liver cells to the hormone insulin. In this state, the liver fails to suppress glucose production and shows decreased glycogen synthesis despite high levels of circulating insulin. This leads to increased hepatic gluconeogenesis and lipid accumulation, contributing significantly to hyperglycemia and dyslipidemia seen in type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD)[1][4][8]. Hepatic insulin resistance is considered a key driver of metabolic diseases but is not itself a single molecule or receptor—it describes an organ-level physiological dysfunction involving multiple molecular pathways including those regulated by transcription factors like FoxO1, CREB, PPAR-alpha, glucocorticoid receptor, as well as epigenetic modifications affecting gene expression[4][2]. Therapeutic strategies focus on modulating these underlying targets rather than "hepatic insulin resistance" per se.

Other names

Impaired hepatic insulin sensitivityLiver insulin resistance