Is phospholipase A2 a "glucose sensor" responsible for the phasic pattern of insulin release?
The mechanisms involved in the characteristic, normal biphasic pattern of glucose-induced insulin release (which is grossly altered in type II diabetics) have not been definitely elucidated. However, the temporal pattern of arachidonic acid release induced by cellular phospholipases precisely mimics that of first-phase insulin release, both being characterized by a burst of release peaking near 2-3 minutes and followed by a "trough" or apparent refractory period most apparent at 5-10 minutes. The latter appears temporally related not only to decreased arachidonate release but also to stimulation of its re-esterification. Pancreatic islets contain a glucose-sensitive phospholipase A2, and glucose has been shown to increase the accumulation of islet lipoxygenase-derived products which appear to be "third messengers" mediating insulin release. Blockade either of islet phospholipase(s) or of islet lipoxygenase totally abrogates glucose-induced insulin release. The hypothesis is therefore proposed that phospholipase A2 could be one beta cell "glucose sensor", and that the released arachidonate is coupled to an islet lipoxygenase. Labile oxygenated metabolites (lipid peroxides and epoxides) transduce the glucose signal into insulin release. The available data (albeit incomplete) are compatible with the formulation that the biphasic pattern of glucose-induced insulin release could be explained by dynamic changes in the availability of arachidonic acid and its consequent oxygenation.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005947:Glucose / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D008954:Models, Biological; D010740:Phospholipases / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2
D001095:Arachidonic Acids; D007328:Insulin; D016718:Arachidonic Acid; D008084:Lipoxygenase; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D005947:Glucose