Islet phospholipase A(2) activation is potentiated in insulin resistant mice.
Insulin resistance is followed by an islet adaptation resulting in a compensating increase in insulin secretion and hyperinsulinemia. The mechanism underlying this increased insulin secretion is not established. We studied whether islet phospholipase A(2) (PLA(2)) contributes by using C57BL/6J mice fed a high-fat diet, since we previously showed that the insulin responses to the two PLA(2)-activating insulin secretagogues carbachol and cholecystokinin (CCK) are enhanced in this model. CCK (100 nM) and carbachol (100 microM) stimulated [(3)H]AA efflux, reflecting PLA(2) activation, both in islets from mice after 12 weeks on high-fat diet and in controls. The efflux increase was more pronounced in islets from high-fat diet-fed mice during both CCK (by 93 +/- 46%; P = 0. 034) and carbachol (by 64 +/- 22%; P = 0.009) stimulation. Also a direct PLA(2) activation by mellitin (2 microg/ml) elicited a potentiated efflux in islets from the insulin-resistant mice (by 361 +/- 107%; P = 0.002). The results suggest that exaggerated non-glucose-induced PLA(2) activation contributes to the islet compensation in insulin resistance.
Simonsson
E
E
Department of Medicine, Lund University, Malmö, Sweden. erik.simonsson@medfork.mas.lu.se
Karlsson
S
S
Ahrén
B
B
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006946:Hyperinsulinism / Q000201:enzymology / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008555:Melitten / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010741:Phospholipases A / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D013997:Time Factors
D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008555:Melitten; D016718:Arachidonic Acid; D002217:Carbachol; D010741:Phospholipases A; D005947:Glucose; D012844:Sincalide