Phospholipid signaling systems in insulin action.
Insulin is known to control a number of anabolic metabolic processes in a variety of target tissues through activation of cell surface receptors. It is clear that insulin receptor activation provokes increases in tyrosine kinase activity and autophosphorylation of the insulin receptor, but subsequent events have not been elucidated. Recently, it has become clear that insulin provokes the following rapid changes in phospholipid metabolism, which result in the generation of several intercellular signaling substances (or mediators): (1) hydrolysis of a phosphatidylinositol-glycan; (2) stimulation of de novo synthesis of phosphatidic acid; and (3) hydrolysis of phosphatidylcholine by a phospholipase C and/or D. Hydrolysis of the phosphatidylinositol-glycan leads to the release of polar headgroups, which serve as mediators to activate phosphatases, and may thereby account for a number of insulin effects on carbohydrate metabolism, lipid metabolism, and regulation of cyclic nucleotide metabolism. All three phospholipid effects of insulin also generate diacylglycerol, which activates protein kinase C, and this may contribute to insulin effects on glucose transport, ion and amino acid transport, protein synthesis, and gene expression (messenger RNA synthesis). Combined, the headgroup mediators and diacylglycerol-protein kinase C signaling systems may account for many, or perhaps most, of insulin's actions. Moreover, the three phospholipid effects of insulin appear to be coordinated, and may function as an integrated cycle to ensure the continued synthesis of lipids, which are the sources of the signaling substances during insulin action.
Farese
R V
RV
James A. Haley Veterans' Hospital, Tampa, Florida 33612.
D000818:Animals; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism
D004075:Diglycerides; D007328:Insulin; D010743:Phospholipids; D011493:Protein Kinase C