Palmitate dependence of insulin secretion, "de novo" phospholipid synthesis and 45Ca2+-turnover in glucose stimulated rat islets.
Palmitate ability to modify D-[U-14C]glucose incorporation into different lipids ("de novo" synthesis), as well as sugar-stimulation of insulin release and 45Ca2+-fluxes, was investigated in islets of fed and 48-h starved rats. The fatty-acid induced dose-dependent, correlative increments of insulin secretion, 45Ca2+-influx and the "de novo" synthesis of each phospholipid fraction analysed at 20 mmol/l (but not 3 mmol/l) glucose. Omission of calcium reduced drastically (p less than 0.001) insulin release and the "de novo" synthesis of neutral glycerolipids, leaving unaltered that of acidic phospholipids (phosphatidate and phosphoinositides). The increased synthesis of the latter is therefore not the consequence of stimulated secretion. It could initiate or contribute to maintain an increased turnover of islet phosphoinositides, thus generating some mediators of the calcium signalling system (inositol phosphates). Starvation led to a drastic reduction (p less than 0.001) of both insulin secretion, "de novo" synthesis of each lipid fraction, and 45Ca2+-influx in response to glucose and palmitate. The presence of a fatty-acid oxidation inhibitor (2-bromostearate or 2-tetradecylglycidate) prevented the effect of starvation on 45Ca2+-influx, as it has been shown to do on insulin secretion and palmitate incorporation into islet lipids. It is finally suggested that palmitate might amplify the insulin secretory response of islets to glucose, through the stimulation of the "de novo" synthesis of phosphoinositides and the subsequent generation of inositol phosphates, which would contribute to accelerated calcium turnover.
Vara
E
E
Department of Biochemistry, Faculty of Medicine, University Complutense, Madrid, Spain.
Fernández-Martín
O
O
García
C
C
Tamarit-Rodríguez
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology*; D010743:Phospholipids / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013217:Starvation
D002132:Calcium Radioisotopes; D010169:Palmitic Acids; D010743:Phospholipids; D019308:Palmitic Acid; D005947:Glucose; D002118:Calcium