Norepinephrine inhibits islet lipid metabolism, 45Ca2+ uptake, and insulin secretion.
We have previously shown that palmitate potentiates, in isolated islets, glucose-induced stimulation of insulin release, "de novo" lipid synthesis, and 45Ca2+ turnover in a correlative manner. Norepinephrine, a known inhibitor of the secretory response, has now been used to further investigate the relationships among the three phenomena. The amine decreased insulin secretion dose dependently in response to glucose and palmitate with alpha 2-adrenergic specificity. It also reduced similarly the oxidation of 1 mmol/l [U-14C]palmitate as well as the incorporation of 20 mmol/l D-[U-14C]glucose into islet phospholipids and neutral lipids through an alpha 2-adrenergic mechanism. These results indirectly suggest that alpha 2-adrenoceptor stimulation inhibits in islets both palmitate oxidation and esterification through an inactivation of long-chain acyl-CoA synthetase and other enzymes of glycerolipid synthesis. Islet uptake of 45Ca2+ was also decreased by norepinephrine with a similar sensitivity to that shown by insulin release and de novo lipid synthesis. Therefore, it is suggested that alpha 2-adrenoceptor-mediated reduction of the potentiation by palmitate of the secretory response to glucose depends on the inhibition of fatty acid metabolism and the resulting impairment of de novo lipid synthesis and 45Ca2+ turnover.
Vara
E
E
Departmento de Bioquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Tamarit-Rodriguez
J
J
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002245:Carbon Dioxide / Q000032:analysis; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D050356:Lipid Metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology
D002132:Calcium Radioisotopes; D007328:Insulin; D010169:Palmitic Acids; D010743:Phospholipids; D002245:Carbon Dioxide; D019308:Palmitic Acid; D015016:Yohimbine; D005947:Glucose; D002118:Calcium; D009638:Norepinephrine