The pancreatic islet as Rubik's Cube. Is phospholipid hydrolysis a piece of the puzzle?
At least three types of phospholipase exist in the beta-cells of the pancreatic islet. Data regarding their physiological activation are incomplete but suggest that glucose (or its metabolite glyceraldehyde) either activates or potentiates the activation of several phospholipases. At least seven phospholipid hydrolysis by-products (diacylglycerol, myo-inositol 1,4,5-trisphosphate, lysophospholipids, arachidonic acid and its cyclooxygenase- and lipoxygenase-derived metabolites, phosphatidate) have been demonstrated to have effects compatible with their postulated roles as mediators or modulators of islet function. Presumptive mechanisms of action have been tentatively identified for these metabolites. However, key studies in the puzzle are missing, and current methodologies have important limitations. Shortcomings include the paucity of measurements of the mass of metabolites; the frequent use of static incubations rather than perfusions; a lack of complete time- and agonist concentration-dependence curves; the equation of metabolite accumulation with rates of metabolite generation (which ignores metabolite removal as a key variable); the use of nonspecific, insensitive, or ambiguous phospholipase assays; and the need for more studies directly correlating lipid metabolism and insulin secretion in physiologically functioning preparations. Like Rubik's Cube, the pancreatic islet is a dynamic puzzle comprised of many interrelated components requiring proper alignment and integration. Phospholipid turnover is one "panel" in the islet; however, an obligate role for phospholipase activation in glucose-induced insulin secretion is not yet rigorously established, despite tantalizing, inferential evidence. It may be that glucose serves principally to potentiate the phospholipase and secretory responses to other signals that act by initiating phospholipid hydrolysis.
Metz
S A
SA
Department of Medicine, University of Wisconsin School of Medicine, Madison.
D000818:Animals; D006868:Hydrolysis; D007515:Islets of Langerhans / Q000502:physiology*; D008954:Models, Biological; D010739:Phospholipase D / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D010743:Phospholipids; D011493:Protein Kinase C; D010741:Phospholipases A; D010738:Type C Phospholipases; D010739:Phospholipase D