Amplification of insulin secretion by lipid messengers.
D-glucose induces a rise in pancreatic islet beta-cell cytosolic [Ca2+] by processes requiring both glucose metabolism and Ca2+ entry from the extracellular space, and this Ca2+ signal is thought to be critical to the induction of insulin secretion. Insulin secretagogues also induce phospholipid hydrolysis and accumulation of phospholipid-derived mediators in islets, including the lipid messengers DAG, nonesterified arachidonic acid, and arachidonate 12-LO products. This study offers the following viewpoints on potential roles of these lipid messengers in insulin secretion as working hypotheses: 1) the Ca2+ signal provided to the beta-cell by D-glucose induces insulin secretion only in the context of amplifying background signals provided by the beta-cell content of messengers including DAG; 2) muscarinic receptor agonists amplify glucose-induced insulin secretion in part by altering the beta-cell content of DAG; 3) the Ca2+ signal provided by metabolism of D-glucose is amplified by the level of nonesterified arachidonic acid in beta-cell membranes, which acts to facilitate Ca2+ entry; 4) metabolism of glucose induces accumulation of nonesterified arachidonate in beta-cells via activation of a recently identified ASCI-PLA2 enzyme, which may be a component of the beta-cell fuel sensor apparatus; and 5) arachidonate 12-LO metabolites are potential candidates as adjunctive modulators of beta-cell K(+)-channel activity.
Turk
J
J
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Gross
R W
RW
Ramanadham
S
S
D000818:Animals; D002118:Calcium / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004075:Diglycerides / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008055:Lipids / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*
C011439:1,2-diacylglycerol; D004075:Diglycerides; D007328:Insulin; D008055:Lipids; D002118:Calcium