Glucose metabolism in mouse pancreatic islets

Abstract

1. Rates of glucose oxidation, lactate output and the intracellular concentration of glucose 6-phosphate were measured in mouse pancreatic islets incubated in vitro. 2. Glucose oxidation rate, measured as the formation of (14)CO(2) from [U-(14)C]glucose, was markedly dependent on extracellular glucose concentration. It was especially sensitive to glucose concentrations between 1 and 2mg/ml. Glucose oxidation was inhibited by mannoheptulose and glucosamine but not by phlorrhizin, 2-deoxyglucose or N-acetylglucosamine. Glucose oxidation was slightly stimulated by tolbutamide but was not significantly affected by adrenaline, diazoxide or absence of Ca(2+) (all of which may inhibit glucose-stimulated insulin release), by arginine or glucagon (which may stimulate insulin release) or by cycloheximide (which may inhibit insulin synthesis). 3. Rates of lactate formation were dependent on the extracellular glucose concentration and were decreased by glucosamine though not by mannoheptulose; tolbutamide increased the rate of lactate output. 4. Islet glucose 6-phosphate concentration was also markedly dependent on extracellular glucose concentration and was diminished by mannoheptulose or glucosamine; tolbutamide and glucagon were without significant effect. Mannose increased islet fructose 6-phosphate concentration but had little effect on islet glucose 6-phosphate concentration. Fructose increased islet glucose 6-phosphate concentration but to a much smaller extent than did glucose. 5. [1-(14)C]Mannose and [U-(14)C]fructose were also oxidized by islets but less rapidly than glucose. Conversion of [1-(14)C]mannose into [1-(14)C]glucose 6-phosphate or [1-(14)C]glucose could not be detected. It is concluded that metabolism of mannose is associated with poor equilibration between fructose 6-phosphate and glucose 6-phosphate. 6. These results are consistent with the idea that glucose utilization in mouse islets may be limited by the rate of glucose phosphorylation, that mannoheptulose and glucosamine may inhibit glucose phosphorylation and that effects of glucose on insulin release may be mediated through metabolism of the sugar.

Tolbutamide potentiates the volume-regulated anion channel current in rat pancreatic beta cells

“…Similarly, the majority of reports suggest that sulphonylureas do not significantly affect the oxidation of 14 C-glucose or the generation of acidic glucose metabolites [30,31,32], at least in long-term incubations. However, an earlier study indicated that tolbutamide increased the oxidation of U-[ 14 C] glucose by 33% and doubled the output of lactate in mouse islets [33]. These findings are essentially consistent with our present findings that tolbutamide caused a 64% increase in the generation of acidic metabolites from glucose.…”

Influence of anoxia on glucose metabolism in pancreatic islets: Lack of correlation between fructose-1,6-diphosphate and apparent glycolytic flux

“…Such studies may also help to explain the puzzling observation that mannoheptulose was a more effective inhibitor of glycolytic flux in oxygenated as compared with anoxic islets. An unexpected behaviour of mannoheptulose is not without precedent, since Ashcroft et al [19] found that the compound markedly inhibited glucose oxidation and yet was without effect on the production of lactate in isolated mouse islets.…”

Effects of hypophysectomy and growth hormone on cultured islets of Langerhans of the rat

“…The 14CO2 was absorbed in hyamine and counted by liquid scintillation spectrometry as described by Ashcroft et al [13]. For measurements of islet content of cyclic AMP, batches of 20islets were first incubated in 10gl bicarbonate-medium containing 2mmol/l of glucose for 10min at 37 ~ and then incubated for a further 2.5 min following addition of 5 lxl medium containing glucose 2 or 50mmol/1.…”