The glycolytic cascade in pancreatic islets

Malaisse, Willy; Malaisse‐Lagae, Francine; Sener, Abdullah

doi:10.1007/bf00257721

Cited by 43 publications

(16 citation statements)

References 37 publications

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“…This situation coincided with a failure of glucose to increase the glucose 1,6-bisphosphate content of islets removed from fasted rats [31]. The data were interpreted, therefore, in support of the view that phosphofructokinase needs to be activated by suitable hexose bisphosphates, in order for the rate of phosphorylation of fructose 6-phosphate to keep pace with its generation rate [33]. In the same perspective, we have recently indicated that the glucose-induced changes in the content of fructose 2,6-bisphosphate in intact islets or purified B ceils are sufficiently marked and sufficiently rapid to indeed participate in the control of phosphofructokinase activity in response to an increase in glucose concentration [341.…”

Section: Physiological and Pathological Dissociation Between Glucokinsupporting

confidence: 62%

Glucokinase is not the pancreatic B-cell glucoreceptor

Malaisse¹,

Sener²

1985

Diabetologia

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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 a-than r-D-glucose. (2) At a high glucose concentration (40 mmol/1), when the phosphorylation of glucose by glucokinase is indeed higher with r-than a-D-glucose, no preference for r-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-laC]glucose, net uptake of 45Ca or release of insulin. (3) The glucose 6-phosphate content of intact islets is higher in the presence oft-than a-D-glucose. (4) At a low glucose concentration (3.3 mmol/1), when the participation of glucokinase to hexose phosphorylation is minimal, a-D-glucose is still better metabolized and stimulates both 45Ca net uptake and insulin release more efficiently than r-D-glucose, despite the fact that hexokinase yields a higher reaction velocity with r-than a-Dglucose. (5) (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. Key words:Pancreatic islets, insulin-producing tumoral cells, glucose anomers, glucokinase, hexokinase.In the 1972 Minkowski Lecture [1], a model was presented for the stimulation of insulin release by nutrient secretagogues and its modulation by polypeptide and adrenergic hormones. The model aimed at illustrating how changes in either the fluxes and intracellular distribution of calcium or generation of cyclic AMP may provide a multifactorial regulation for a single process of release, as mediated by the microtubular-microfilamentous effector system. In addition, it was briefly proposed, at variance with a current view at that time [2,3], "that glucose has to be transported and metabolized in the B cell in order to stimulate insulin secretion". In further work, my colleagues and I concentrated mainly on the validity of the latter proposal. We eventually reached the conclusion that the insulinotropic action of nutrient secretagogues indeed reflects their capacity to augment oxidative fluxes in the islet cells, this being defined as the fuel hypothesis [4] or fuel concept [5] for insulin release.One of the essential arguments in support of this fuel concept consisted of the finding that the higher insulinotropic capacity of the a-than fl-anomer of either Dglucose or D-mannose coincides with a higher rate of glycolysis in pancreatic islets exposed to the a-as distinct from fl-anomer of these two ...

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Section: Physiological and Pathological Dissociation Between Glucokinsupporting

confidence: 62%

Glucokinase is not the pancreatic B-cell glucoreceptor

Malaisse¹,

Sener²

1985

Diabetologia

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“…Consistent with the results obtained from Malaisse et al [30] and Colomer et al [31], our results demonstrated elevation of PFK-1 activity in AsPC-1 cells pretreated with D-glucose or D-fructose. The roles of these hexoses in the metabolism of cancer cells have been thoroughly investigated.…”

Section: Discussionsupporting

confidence: 93%

A strategy for improving FDG accumulation for early detection of metastasis from primary pancreatic cancer: Stimulation of the Warburg effect in AsPC-1 cells

Ogura

Shikano

Nakajima

et al. 2015

Nuclear Medicine and Biology

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a b s t r a c t a r t i c l e i n f oIntroduction: Early detection and/or prediction of metastasis provide more prognostic relevance than local recurrence. Direct spread into the peritoneum is frequently found in pancreatic cancer patients, but positron emission tomography (PET) with 2-deoxy-2-fluoro-D-glucose (FDG) is not useful for identifying such metastasis. We investigated a method to enhance FDG accumulation using AsPC-1 human ascites tumor cells. Methods: 14 C-FDG accumulation was assessed under the following conditions: 1) characteristics of 14 C-FDG transport were examined using phloridzin, a Na + -free buffer, and various hexoses, and 2) accumulation of 14 C-FDG was measured in cells that were pretreated with hexose for various time periods, and activity of 6-phosphofructo-1-kinase (PFK-1) was assayed.

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“…In this respect, thé most salient finding in this study, namely thé vastly différent Hill number for each of thèse anomers, should now be integrated in thé scheme previously proposed to account for thé respective contribution of a-and /3-Dglucose to thé overall rate of D-glucose phosphorylation by glucokinase when thé hexose is présent at anomeric equilibrium (43). This is most relevant to thé régula-tion of D-glucose metabolism in hepatocytes and B-cells since each of thé two anomers of D-glucose 6-phosphate may be preferentially channelled into distinct pathways (44,45).…”

Section: Discussionmentioning

confidence: 99%

Anomeric Specificity of Human Liver and B-cell Glucokinase: Modulation by the Glucokinase Regulatory Protein

Courtois¹,

Bource²,

Sener³

et al. 2000

Archives of Biochemistry and Biophysics

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The anomeric specificity of thé wild-type recombinant forms of human liver and B-cell glucokinase was investigated using radioactive anomers of D-glucose as tracers. With D-glucose at anomeric equilibrium and at 30°C, thé maximal velocity, Hill number, and K, amounted, respectively, to 16 /.unol min"1 mg"1,1.8 and 6.9 mM in thé case of liver glucokinase, and 7. The anomeric specificity of liver and pancreatic islet glucokinase was examined by several investigators (1-5). Interest in this matter is motivated inter alla by thé knowledge that, under physiological conditions, a-Dglucose is a more potent insulin secretagog than /3-Dglucose (6-10). Because of thé key rôle played by glucokinase in thé régulation of D-glucose metabolism in islet insulin-producing cells (11), thé question was raised whether thé anomeric specificity of B-cell glucokinase may indeed account for thé higher insulinotropic capacity of a-D-glucose (4, 5). Moreover, in noninsulin-dependent diabètes mellitus, thé préférence of thé B-cell secretory response for a-relative to /3-Dglucose is often decreased and may even be inverted (12-16). Although such a perturbation, which can be reproduced in normal rats through sustained hyperglycemia caused by either thé administration of diazoxide (17) or partial pancreatectomy (18), appears usually attributable to glycogen accumulation in thé pancreatic islet cells (19), a mutation of thé glucokinase gène resulting in an altered anomeric behavior of thé enzyme, was also considered as a possible and exceptional cause for thé anomeric malaise in insulin sécré-tion (20).In intact B-cells, however, thé phosphorylation of D-glucose is not ruled solely by thé cytosolic concentration of thé hexose and thé intrinsic properties of glucokinase and hexokinase. It can also be affected by a number of other factors, such as thé concentration of ATP and D-glucose 6-phosphate (21, 22), thé binding of thé hexokinase isoenzymes to mitochondrial porin (23-25), thé modulation of glucokinase activity by its reg-126

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The glycolytic cascade in pancreatic islets

Cited by 43 publications

References 37 publications

Glucokinase is not the pancreatic B-cell glucoreceptor

Glucokinase is not the pancreatic B-cell glucoreceptor

A strategy for improving FDG accumulation for early detection of metastasis from primary pancreatic cancer: Stimulation of the Warburg effect in AsPC-1 cells

Anomeric Specificity of Human Liver and B-cell Glucokinase: Modulation by the Glucokinase Regulatory Protein

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