Impaired enzyme-to-enzyme channelling between hexokinase isoenzyme(s) and phosphoglucoisomerase in rat pancreatic islets incubated at a low concentration ofD-glucose

Abstract

It was recently proposed that in rat pancreatic islets exposed to 8.3 mM D-glucose, alpha-D-glucose-6-phosphate undergoes enzyme-to-enzyme channelling between hexokinase isoenzyme(s) and phosphoglucoisomerase. To explore the identity of the hexokinase isoenzyme(s) involved in such a tunnelling process, the generation of 3HOH from the alpha- and beta-anomers of either D-[2-3H]glucose or D-[5-3H]glucose was now measured over 60 min incubation at 4 degrees C in pancreatic islets exposed only to 2.8 mM D-glucose, in order to decrease the relative contribution of glucokinase to the phosphorylation of the hexose. Under these experimental conditions, the ratio for 3HOH production from D-[2-3H]glucose/D-[5-3H]glucose at anomeric equilibrium (39.7 +/- 11.6%) and the beta/alpha ratios for the generation of 3HOH from either the D-[2-3H]glucose anomers (70.9 +/- 12.6%) or the D-[5-3H]glucose anomers (59.6 +/- 12.4%) indicated that a much greater fraction of alpha-D-glucose-6-phosphate escapes from the process of enzyme-to-enzyme channelling in the islets exposed to 2.8 mM, rather than 8.3 mM D-glucose. These findings suggest, therefore, that the postulated process of enzyme-to-enzyme channelling involves mainly glucokinase.

Anomeric specificity of D-glucose metabolism study in rat and human erythrocytes

“…In conclusion, the present results, when compared to those recently collected in rat pancreatic islets [33,34], document that the channeling of α-D-glucose 6-phosphate from its site of generation to phosphoglucoisomerase is affected in opposite manner by a rise in hexose concentration in rat erythrocytes versus rat pancreatic islets. Such contrasting situations support the view that the regulation of the enzyme-to-enzyme tunneling process tightly depends on the identity of the hexokinase isoenzyme (low-Km hexokinase versus high Km glucokinase) mainly responsible for the phosphorylation of Dglucose in distinct cell types.…”

L‐glutamine and palmitate catabolism in pancreatic islets from rats depleted in long‐chain polyunsaturated ω3 fatty acids

“…Moreover, the fact that the net uptake of [U- 14 C]palmitate and absolute value for 14 CO 2 output by islets prelabelled with the same nutrient were both increased in v3-depleted rats affords further support to the proposal that the impaired metabolism of D-glucose in the islets of these animals may be attributable, at least in part, to an increase in the acyl CoA content of islet cells. 3 However, considering the multiple modalities of interaction between the metabolism of D-glucose, L-glutamine and fatty acids, [15][16][17] further investigations on the intracellular content of such metabolites as neutral lipids, acyl-CoA, acetyl-CoA, citrate and D-glucose-6-phosphate under the present experimental conditions would be necessary to validate the above proposals.…”