Effects of lactate on pancreatic islets. Lactate efflux as a possible determinant of islet-cell depolarization by glucose.
The secretion of insulin from perifused rat pancreatic islets was stimulated by raising the glucose concentration from 5.6 to 20 mM or by exposure to tolbutamide. The addition of sodium lactate (40 mM) to islets perifused in the presence of glucose (5.6 mM) resulted in a small, transient, rise in the rate of secretion. The subsequent removal of lactate, but not glucose or tolbutamide, from the perifusate produced a dramatic potentiation of insulin release. The rate of efflux of 45Ca2+ was also increased when islets were exposed to a high concentration of glucose or lactate or to tolbutamide, and again subsequently upon withdrawal of lactate. Efflux of 86Rb+ was modestly inhibited upon addition of lactate and markedly enhanced by the subsequent withdrawal of lactate from islets. The output of [14C]lactate from islets incubated in the presence of [U-14C]glucose increased linearly with increasing concentrations of glucose (1-25 mM). It is proposed that the activation of islets by the addition or withdrawal of lactate is not due to increased oxidative flux, but occurs as a result of the electrogenic passage of lactate ions across the plasma membrane, resulting in islet-cell depolarization, Ca2+ entry and insulin secretion. The production of lactate via the glycolytic pathway, and the subsequent efflux of lactate from the islet cells with concomitant exchange of H+ for Na+, could be a major determinant of depolarization and hence insulin secretion, in response to glucose.
Best
L
L
Department of Medicine, University of Manchester, U.K.
Yates
A P
AP
Meats
J E
JE
Tomlinson
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D014044:Tolbutamide / Q000494:pharmacology
D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D014044:Tolbutamide; D005947:Glucose; D002118:Calcium