Summary
A series of recent experimental findings are reviewed to indicate that glucokinase does not represent the pancreatic B-cell glucoreceptor. (1) Whether in liver, pancreatic islet or insulin-producing tumoral cell homogenates, glucokinase fails to yield a higher reaction velocity with α-than β-D-glucose. (2) At a high glucose concentration (40 mmol/l), when the phosphorylation of glucose by glucokinase is indeed higher with β- than α-D-glucose, no preference for β-D-glucose is observed in intact islets, as judged from the utilization of D-[5-3H]glucose, production of lactic acid, oxidation of D-[U-14C] glucose, net uptake of 45Ca or release of insulin. (3) The glucose 6-phosphate content of intact islets is higher in the presence of β- than α-D-glucose. (4) At a low glucose concentration (3.3 mmol/l), when the participation of glucokinase to hexose phosphorylation is minimal, α-D-glucose is still better metabolized and stimulates both 45Ca net uptake and insulin release more efficiently than β-D-glucose, despite the fact that hexokinase yields a higher reaction velocity with β- than α-D-glucose. (5) In intact islets, β-D-glucose is used preferentially to α-D-glucose in the pentose cycle pathway as judged from the oxidation of α- or β-D-[1-14C]glucose relative to that of α- or β-D-[6-14C]glucose. (6) In islets removed from fasted rats, the rate of glycolysis is more severely decreased than expected from the repression of glucokinase. (7) The metabolism of glucose in tumoral insulin-producing cells differs, in several respects, from that in normal pancreatic islets, although the pattern of hexokinase and glucokinase activities is similar in these two types of cells. All these observations point to the participation of regulatory sites distal to glucose phosphorylation in the control of glucose metabolism in islet cells.
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Malaisse, W.J., Sener, A. Glucokinase is not the pancreatic B-cell glucoreceptor. Diabetologia 28, 520–527 (1985). https://doi.org/10.1007/BF00281986
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DOI: https://doi.org/10.1007/BF00281986