Chlorpropamide Raises Fructose-2,6-Bisphosphate Concentration and Inhibits Gluconeogenesis in Isolated Rat Hepatocytes

doi:10.2337/diab.35.1.89

Paper

Chlorpropamide Raises Fructose-2,6-Bisphosphate Concentration and Inhibits Gluconeogenesis in Isolated Rat Hepatocytes

Published Jan 1, 1986 · L. Monge, M. Mojena, J. Ortega

Diabetes

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35

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0

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Abstract

The addition of chlorpropamide to hepatocytes isolated from fed rats raised the cellular concentration of fructose-2,6-bisphosphate (F-2,6-P2), a regulatory metabolite that plays a relevant role in the control of hepatic glucose metabolism. The effect of chlorpropamide was dose dependent; a statistically significant increase was already seen at 0.2 mM of the sulfonylurea. The accumulation of F-2,6-P2 caused by chlorpropamide (1 mM) was parallel to the stimulation of L-lactate production (36.6 ± 4.8 versus 26.1 ± 2.6 μmol of lactate/g of cells × 20 min; N = 5, P < 0.05) and to the inhibition of gluconeogenesis (0.57 ± 0.1 versus 0.94 ± 0.09 μmol of [U-14C]pyruvate converted to glucose/g of cells × 20 min; N = 5, P < 0.05). In addition, chlorpropamide enhanced the inhibitory action evoked by insulin on glucagon-stimulated gluconeogenesis. This combined effect of chlorpropamide and insulin seems to be correlated with the synergistic accumulation of F-2,6-P2provoked by the simultaneous action of these two agents on glucagon-treated hepatocytes. Finally, neither 6-phosphofructo-2-kinase activity nor hepatocyte cyclic AMP levels were significantly changed by the presence of the sulfonylurea in the incubation medium. Our results support the concept that chlorpropamide, by a cyclic AMP-independent mechanism, increases the hepatic content of F-2,6-P2 and, in this way, enhances the glycolytic flux and inhibits glucose output by the liver.

In Vitro Study

Study Snapshot

Chlorpropamide increases fructose-2,6-bisphosphate concentration in rat hepatocytes, enhancing glycolytic flux and inhibiting glucose output without affecting cyclic AMP levels.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Chlorpropamide Raises Fructose-2,6-Bisphosphate Concentration and Inhibits Gluconeogenesis in Isolated Rat Hepatocytes

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References

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