Overexpression of lactate dehydrogenase A attenuates glucose-induced insulin secretion in stable MIN-6 beta-cell lines.

Since islet beta-cells express little L-lactate dehydrogenase (LDH) activity, we have examined the effects on these cells of LDH overexpression. In mock-transfected MIN6 beta-cells, LDH activity was 38 nmol/min/mg protein, and 30 mM glucose stimulated secretion 10.4-fold. In two MIN6 cell clones stably overexpressing human LDH-A cDNA, insulin secretion was stimulated only 2.7- and 2.1-fold by high glucose. K+-stimulated insulin secretion was unaffected, and leucine stimulation enhanced, by LDH-A overexpression. LDH-A-overexpressing clones displayed unaltered activities of hexokinase, glucokinase, and malate dehydrogenase, slightly elevated plasma membrane lactate transport activity, and lowered insulin content. Low LDH activity would therefore appear important in beta-cell glucose sensing.