OXYGEN CONSUMPTION OF THE β-CELLS IN RELATION TO INSULIN RELEASE*

SUMMARY The oxygen consumption and the 14 CO 2 -production by isolated and surviving islets of Langerhans from obese-hyperglycaemic mice was studied. Sufficient analytical sensitivity was achieved by incubating islets in Cartesian divers in which changes in the gas volume of the order of 0.5 nl could be measured. One to five microdissected islets corresponding to a total dry weight of 1–20 μg were sufficient for an experiment. In obese-hyperglycaemic mice the islets are composed to more than 90% of β-cells, and each μg of dry weight of islet tissue contains about 5000 β-cells. The endogenous respiratory rate of islets incubated in Krebs-Ringer phosphate buffer was constant for several hours. Addition of glucose brought about a rapid and pronounced stimulation of the respiratory rate; a smaller degree of stimulation was observed with mannose and fructose. There was no effect of galactose, l -glucose, 2-deoxyglucose, allose, altrose, tagatose, talose, xylose, lyxose, l -arabinose, fucose, or xylitol. A slight inhibition was recorded with mannoheptulose and glucosamine. The latter substances, as well as 6-deoxyglucose, altrose, talose, malonate and iodoacetate also suppressed the respiration of islets pre-incubated with glucose. Among the Krebs’ cycle intermediates tested only citrate, succinate, and oxaloacetate enhanced the respiratory rate. Addition of amino acids showed that valine and arginine failed to affect the oxygen consumption, whereas a significant stimulation was obtained with both alanine and leucine. Hormonal effects on the islet respiration were demonstrated with glucagon and adrenaline which both inhibited the oxygen uptake. Preliminary experiments suggested that dibutyryl 3′,5′-cyclic-AMP had a similar effect. A modification of the diver technique made possible the assay of 14 CO 2 -production from 14 C-labelled precursors. The yield of 14 CO 2 from glucose-U- 14 C increased with the glucose concentration and was suppressed by mannoheptulose. The 14 CO 2 production from 14 C-labelled l -leucine indicated a substantial rate of decarboxylation of this amino acid by the pancreatic β-cells.