Lactate alters plasma membrane potential, increases the concentration of cytosolic Ca2+ and stimulates the secretion of insulin by the hamster beta-cell line HIT-T15.
We have studied the effect of lactate on a number of intracellular events which may be important in controlling the secretion of insulin by the hamster beta-cell line HIT-T15. Using the fluorescent dye Oxonol V, as well as intracellular recording techniques to measure changes in membrane potential, we found that lactate, glucose, K+ and tolbutamide caused depolarization of HIT cells, while valinomycin resulted in hyperpolarization. Consistent with these findings was the observation that 10 mM lactate caused an increase of 69.0 +/- 18.4% (S.E.M., n = 6) in the level of free cytosolic Ca2+ within HIT cells (assessed by fluorescence of quin 2). This was probably due to influx of Ca2+ through voltage-sensitive calcium channels, since it was dependent upon the concentration of extracellular Ca2+ and inhibited by verapamil. Lactate also caused cytosolic acidification in HIT cells and increased the secretion of insulin. These findings are consistent with the view that the electrogenic efflux of lactate could be a determinant in the activation of HIT cells by lactate and possibly by glucose.
Meats
J E
JE
Department of Medicine, University of Manchester.
Tuersley
M D
MD
Best
L
L
Lynch
A M
AM
Tomlinson
S
S
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000085:Acetates; D007328:Insulin; D007773:Lactates; D014634:Valinomycin; D019344:Lactic Acid; D014044:Tolbutamide; D014700:Verapamil; D005947:Glucose; D019342:Acetic Acid; D011188:Potassium; D002118:Calcium