Glucokinase as Glucose Sensor and Metabolic Signal Generator in Pancreatic β-Cells and Hepatocytes

This article reviews evidence for a pivotal role of glucokinase as glucose sensor of the pancreatic β-cells. Glucokinase explains the capacity, hexose specificity, affinities, sigmoidicity, and anomeric preference of pancreatic islet glycolysis, and because stimulation of glucose metabolism is a prerequisite of glucose stimulation of insulin release, glucokinase also explains many characteristics of this β-cell function. Glucokinase of the β-cell is induced or activated by glucose in contrast to liver glucokinase, which is regulated by insulin. Tissue-specific regulation corresponds with observations that liver and pancreatic β-cell glucokinase are structurally distinct. Glucokinase could play a glucose-sensor role in hepatocytes as well, and certain forms of diabetes mellitus might be due to glucokinase deficiencies in pancreatic β-cells, hepatocytes, or both.

[1]  M. Magnuson,et al.  An alternate promoter in the glucokinase gene is active in the pancreatic beta cell. , 1989, The Journal of biological chemistry.

[2]  R. Printz,et al.  Rat glucokinase gene: structure and regulation by insulin. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D. Hanahan,et al.  Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[4]  H. Najafi,et al.  Control of Glucose Metabolism in Pancreatic β-Cells by Glucokinase, Hexokinase and Phosphofructokinase: Model Study With Cell Lines Derived From β-Cells , 1988, Diabetes.

[5]  F. Matschinsky,et al.  Control of Glucose Phosphorylation and Glucose Usage in Clonal Insulinoma Cells , 1988, Diabetes.

[6]  F M Matschinsky,et al.  Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion. , 1987, Physiological reviews.

[7]  F. Matschinsky,et al.  Glucokinase in B-cell-depleted islets of Langerhans. , 1987, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[8]  C. Newgard,et al.  From dietary glucose to liver glycogen: the full circle round. , 1987, Annual review of nutrition.

[9]  H. Najafi,et al.  Acetylcholine stimulates glucose metabolism by pancreatic islets. , 1986, Life sciences.

[10]  F. Matschinsky,et al.  Differential regulation of glucokinase activity in pancreatic islets and liver of the rat. , 1986, The Journal of biological chemistry.

[11]  D. Finegold,et al.  The Glucokinase Glucose Sensor in Human Pancreatic Islet Tissue , 1986, Diabetes.

[12]  F. Matschinsky,et al.  Pancreatic islet glucose metabolism and regulation of insulin secretion. , 1986, Diabetes/metabolism reviews.

[13]  D. W. Foster.  From Glycogen to Ketones—And Back , 1984, Diabetes.

[14]  J. McGarry,et al.  The glucose paradox. Is glucose a substrate for liver metabolism? , 1984, The Journal of clinical investigation.

[15]  F. Matschinsky,et al.  New perspectives on pancreatic islet glucokinase. , 1984, The American journal of physiology.

[16]  J. McGarry,et al.  In vitro reversal of the fasting state of liver metabolism in the rat. Reevaluation of the roles of insulin and glucose. , 1981, The Journal of clinical investigation.

[17]  F. Bontemps,et al.  Phosphorylation of glucose in isolated rat hepatocytes. Sigmoidal kinetics explained by the activity of glucokinase alone. , 1978, Biochemical Journal.

[18]  S. Weinhouse,et al.  Regulation of glucokinase in liver. , 1976, Current topics in cellular regulation.

[19]  H G Hers,et al.  The control of glycogen metabolism in the liver. , 1976, Annual review of biochemistry.

[20]  H. Hers,et al.  The interaction of liver phosphorylase a with glucose and AMP. , 1974, European journal of biochemistry.

[21]  E. Taylor,et al.  Glycogen synthesis in the perfused liver of the starved rat. , 1971, The Biochemical journal.

[22]  H. Hers,et al.  The control of glycogen metabolism in the liver , 1970, FEBS letters.

[23]  F. Matschinsky,et al.  Metabolism of glucose in the islets of Langerhans. , 1968, The Journal of biological chemistry.

[24]  F. Ballard.  GLUCOSE UTILIZATION IN MAMMALIAN LIVER. , 1965, Comparative biochemistry and physiology.