Peripheral Tissue Insulin Sensitivity Pathway

The peripheral tissue insulin sensitivity pathway refers to the molecular signaling cascade by which insulin regulates glucose uptake, metabolism, and storage in peripheral tissues—primarily skeletal muscle, adipose (fat) tissue, and liver. Key components include the Insulin Receptor (INSR), Insulin Receptor Substrates (IRS1/2), and downstream signaling pathways like PI3K–Akt/PKB and MAPK. Tissue-specific actions involve glucose uptake/storage in muscle, suppression of lipolysis/lipid storage in adipose tissue, and suppression of gluconeogenesis/glycogen/lipid synthesis in the liver. Regulation occurs via negative feedback, dephosphorylation, and receptor internalization. Peripheral tissue insulin resistance is a hallmark of type 2 diabetes and obesity. Therapeutic modulation includes drugs like metformin and lifestyle interventions like exercise.

Enhancement of insulin sensitivity in peripheral tissues