Insulin second messengers

Abstract

The molecular pathways for insulin's signal transduction from its cell surface receptor to the cell's interior metabolic machinery remain in many ways uncharted. Lately two molecules have been proposed as second messengers transducing the insulin signal into the target cell. One is a phospho-oligosaccharide/inositolphosphoglycan and the other is diacylglycerol, both deriving from the same plasma membrane glycolipid, which is hydrolysed in response to insulin treatment. The phospho-oligosaccharide appears to mediate many metabolic effects of insulin through control of the phosphorylation state of key regulatory metabolic enzymes. Diacylglycerol may mediate insulin's stimulation of glucose transport over the plasma membrane. The glycolipid precursor of these putative second messengers, as well as the receptor for insulin, appear to be localized in caveolae microdomains of the plasma membrane, and glucose transporters accumulate in caveolae in response to insulin treatment, suggesting a focal role for caveolae in insulin signalling.

The Caveolae Membrane System

“…Sphingomyelin, phosphatidylinositol 4,5, bisphosphate, and GPI proteins/lipids are substrates for enzymes that release ceramide (82,191), inositol trisphosphate (IP3) (192,193), and inositolphosphoglycans (IPG) (194,195), respectively. Each is produced in caveolae after a specific stimuli.…”

Insulin inhibits phagocytosis in normal human neutrophils via PKCα/β-dependent priming of F-actin assembly

“…Further downstream signaling events may include PI3-kinase, p21 ras and MAP kinase, each involved in a big array of the cellular effects of insulin [8]. However, some effects of insulin have been suggested to be mediated by other signaling pathways, perhaps involving insulin receptor-mediated non-covalent activation of G proteins with subsequent PLC-dependent generation of inositolphosphoglycan (IPG) and DAG [9,10]. Thus, IPG and DAG, with or without the involvement of PKC, have booth been implicated as second messengers of insulin [9].…”

“…However, some effects of insulin have been suggested to be mediated by other signaling pathways, perhaps involving insulin receptor-mediated non-covalent activation of G proteins with subsequent PLC-dependent generation of inositolphosphoglycan (IPG) and DAG [9,10]. Thus, IPG and DAG, with or without the involvement of PKC, have booth been implicated as second messengers of insulin [9]. We have previously reported that insulin could stimulate chemokinesis in adherent neutrophils, an effect that was sensitive to inhibitors of PI3 kinase and tyrosine kinases [6].…”

“…The stimulating effect of insulin on neutrophil motility was found to be mediated through a tyrosine kinase and PI3-kinase-dependent signaling pathway [6]. Although most effects of insulin are thought to be dependent on tyrosine kinase activity and PI3-kinase activity [8], there is also evidence for insulin receptor signaling pathways involving phopsholipase C (PLC), diacylglycerol (DAG) and protein kinase C (PKC) [9,10].…”

Acceleration of early chick embryo morphogenesis by insulin is associated with altered expression of embryonic genes

“…3). Transduction of signal after the binding of insulin-related ligands to receptors results in the classic anabolic effects of insulin (reviewed by Stralfors, 1997). Insulin is also known to be a mitogen (Harvey and Kaye, 1990;Gardner and Kaye, 1991).…”