We assessed our speculation that 2-cyclohexen-1-one (CHX) impairs glucose-induced insulin secretion through inactivation of glucokinase. Treatment of pancreatic islets with CHX at concentrations (0–5 mM) that caused a dose-dependent inactivation of glucokinase activity similarly inhibited glucoseinduced insulin secretion. Another glucosephosphorylating enzyme (hexokinase) in pancreatic islets was little affected by CHX. CHX-induced inactivation of glucokinase was blocked by the presence of its substrates (glucose and mannose) and an inhibitor (N-acetylglucosamine), all of which also protected against the inhibitory effect of the drug on glucose-induced insulin secretion. CHX also impaired insulin secretion induced by D-glyceraldehyde and dimethyl succinate, which are believed to stimulate the release of the hormone by being directly oxidized by glyceraldehyde-3-phosphate dehydrogenase, by entering the midstream of the glycolytic pathway as glyceraldehyde 3-phosphate, or by entering the tricarboxylic acid cycle in mitochondria after intracellular hydrolysis. The inhibitory effect of CHX on glucose-induced insulin secretion, however, was far more marked than that on insulin secretion evoked by D-glyceraldehyde and dimethyl succinate at any CHX concentrations used. Our study revealed that the inhibitory action of CHX on glucose-induced insulin secretion is exerted mainly, but not solely, through inactivation of glucokinase. This conclusion supports the view that glucokinase is a key enzyme in the recognition of glucose as an insulin secretagogue in pancreatic islets.
Participation of Glucokinase Inactivation in Inhibition of Glucose-Induced Insulin Secretion by 2-Cyclohexen-1-One
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Ichitomo Miwa, Tomiyasu Murata, Sachie Mitsuyama, Jun Okuda; Participation of Glucokinase Inactivation in Inhibition of Glucose-Induced Insulin Secretion by 2-Cyclohexen-1-One. Diabetes 1 October 1990; 39 (10): 1170–1176. https://doi.org/10.2337/diab.39.10.1170
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