Insulin is a 51-amino acid peptide hormone that is synthesized and secreted by pancreatic beta cells (table 1). This topic will review the metabolic actions of insulin. The structure and function of the insulin receptor and details of insulin secretion are reviewed separately. (See "Structure and function of the insulin receptor" and "Insulin secretion and pancreatic beta-cell function".)
Insulin action begins with the binding of insulin to a heterotetrameric receptor on the cell membrane of the target cells. Insulin receptors are membrane glycoproteins composed of two separate insulin-binding (alpha-subunits) and two signal transduction (beta-subunits) domains. Binding of insulin to the receptor results in conformational change of the alpha-subunits that enables ATP binding to the beta-subunit’s intracellular domain. ATP binding leads to activation of a tyrosine kinase in the beta-subunit that autophosphorylates the receptor. The phosphorylated receptor in turn phosphorylates other protein substrates beginning with insulin-receptor substrate (IRS) 1 and 2 [1-4]. The insulin signal is further propagated through a phosphorylation network involving other intracellular substances. The biochemistry of insulin action is reviewed in detail separately. (See "Structure and function of the insulin receptor".)
Through activation of these signaling pathways, insulin acts as a powerful regulator of metabolic function. Furthermore, insulin receptor-mediated activation of the mitogen-activated protein (MAP) kinase pathway has been implicated in insulin's effects on growth and proliferation .
Of clinical relevance, defects in insulin signaling have been demonstrated in several of the insulin resistance syndromes. (See "Insulin resistance: Definition and clinical spectrum".)
METABOLIC EFFECTS OF INSULIN
Insulin directly or indirectly affects the function of virtually every tissue in the body. However, in this brief overview we will focus on insulin's metabolic effects on the three tissues most responsible for energy storage: liver, muscle, and adipose tissue (table 2).