In terms of glucose sensing by pancreatic islet β-cells, emphasis is currently placed on both the role of glucokinase, with negligible activity of low-Km hexokinase(s), and the prevalence of the oxidative over non-oxidative modality of glycolysis, a situation tentatively attributed, in part at least, to a low activity of lactate dehydrogenase. Conflicting information is available, however, on the activity of both low-Km hexokinase(s) and lactate dehydrogenase in purified β-cell homogenates. This issue was reinvestigated, therefore, in two populations of purified rat islet β-cells selected on the basis of their low (βL) or high (βH) content in reduced pyridine nucleotides. The size and protein content of βH cells represented about twice that of βL cells. Such was also the case for low-Km hexokinase(s), lactate dehydrogenase, mitochondrial FAD-linked glycerophosphate dehydrogenase, glutamate dehydrogenase and glutamate-alanine and glutamate-aspartate transaminases. Whether in βH or βL cells, the activity of low-Km hexokinase(s) was at least as high as or higher than that of glucokinase. In both βH and βL, the activity of lactate dehydrogenase exceeded that required to catalyze the full reduction of glucose-derived pyruvate to L-lactate, as estimated from the rate of D-glucose phosphorylation under physiological conditions. These findings thus argue against a low expression of either low-Km hexokinase(s) or lactate dehydrogenase as major determinants of the glucose-sensing device in β-cells.

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