Mannose Phosphorylation by Glucokinase from Liver and Transplantable Insulinoma: Cooperativity and Discrimination of Anomers

Meglasson, M. D.; Schinco, Miren A.; Matschinsky, Franz M.

doi:10.2337/diab.32.12.1146

Cited by 17 publications

(10 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this respect, the situation found in adipocytes is similar to that recently characterized in both normal and tumoral pancreatic islet cells [7]. These converging findings clearly document that the anomeric specificity of hexose metabolism cannot be accounted for solely by differences in either the rate of transport of each anomer into the cell or their respective rate of phosphorylation, at variance with a recent proposal [17,181. The preferential utilization of a-D-glucose 6-phosphate in the glycolytic pathway and the mixed @glucose anomers ( x 1.5 m M a and x 2.5 m M p) preferential orientation of p-D-glucose 6-phosphate into the pentose cycle indeed indicate that the anomeric specificity of phosphoglucose isomerase, which is a-stereospecific, and that of glucose-6-phosphate dehydrogenase, which is p-stereospecific, are both operative in intact cells.…”

Section: Discussioncontrasting

confidence: 53%

Anomeric specificity of D‐glucose metabolism in rat adipocytes

Malaisse‐Lagae

Malaisse

1986

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 53%

Anomeric specificity of D‐glucose metabolism in rat adipocytes

Malaisse‐Lagae

Malaisse

1986

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…In contrast, hexokinase IV, more commonly known as glucokinase (GK), is about half the molecular mass, has a KcatSOs that is similar to the blood glucose concentration, displays sigmoidal kinetics, and is not significantly affected by physiological concentrations of G6P. These unique kinetic features of GK have long been thought to be of key functional significance in the liver and pancreatic p cell, two sites where the enzyme has been known for years to be expressed (Weinhouse, 1976;Meglasson and Matschinsky, 1983). The predicted functional importance of this enzyme in these cell types has led to intensive investigation, both in humans and in animal model systems, to understand the role of GK in determining the setpoint for the blood glucose concentration.…”

Section: Kinetic Behavior and Tissue-specific Functions Of Glucokimentioning

confidence: 99%

Cell-specific Roles of Glucokinase in Glucose Homeostasis

Postic

Shiota²,

Magnuson³

2001

Recent Progress in Hormone Research

149

128

View full text Add to dashboard Cite

Mutations in the glucokinase (GK) gene cause two different diseases of blood glucose regulation: maturity onset diabetes of the young, type 2 (MODY-2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI). To gain further understanding of the pathophysiology of these disorders, we have used both transgenic and gene-targeting strategies to explore the relationship between GK gene expression in specific tissues and the blood glucose concentration.These studies, which have included the use of a CrelloxP gene-targeting strategy to perform both pancreatic g-cell-and hepatocyte-specific knockouts of GK, clearly demonstrate multiple, cell-specific roles for this hexokinase that, together, contribute to the maintainance of euglycemia.In the pancreatic g cell, GK functions as the glucose sensor, determining the threshold for insulin secretion, Mice lacking GK in the pancreatic l3 cell die within 3 days of birth of profound hyperglycemia.In the liver, GK facilitates hepatic glucose uptake during hyperglycemia and is essential for the appropriate regulation of a network of glucose-responsive genes. While mice lacking hepatic GK are viable, and are only mildly hyperglycemic when fasted, they also have impaired insulin secretion in response to hyperglycemia.The mechanisms that enable hepatic GK to affect +ell function are not yet understood. Thus, the hyperglycemia that occurs in MODY-2 is due to impaired GK function in both the liver and pancreatic g cell, although the defect in g-cell function is clearly more dominant, Whether defects in GK gene expression also impair glucose sensing by neurons in the brain or enteroendocrine cells in gut, two other sites known to express GK, remains to be determined. Moreover, whether the pathophysiology of PHHI also involves multitissue dysfunction remains to be explored.

show abstract

“…We attributed such a metabolic difference to the anomeric specificity of phosphoglucose isomerase and phosphoglucomutase, as reviewed in detail elsewhere [8]. Recently, however, Matschinsky et al proposed that the anomeric specificity of hexose metabolism in islet cells is attributable to a limited preference of glucokinase for the ct-anomer of either D-glucose or D-mannose [9,10]. The latter claim was considered in the framework of the concept that glucokinase would act as a glucoreceptor in the pancreatic B-cell [11,12].…”

mentioning

confidence: 99%

Glucokinase is not the pancreatic B-cell glucoreceptor

Malaisse¹,

Sener²

1985

Diabetologia

View full text Add to dashboard Cite

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 ...

show abstract

Mannose Phosphorylation by Glucokinase from Liver and Transplantable Insulinoma: Cooperativity and Discrimination of Anomers

Cited by 17 publications

References 13 publications

Anomeric specificity of D‐glucose metabolism in rat adipocytes

Anomeric specificity of D‐glucose metabolism in rat adipocytes

Cell-specific Roles of Glucokinase in Glucose Homeostasis

Glucokinase is not the pancreatic B-cell glucoreceptor

Contact Info

Product

Resources

About