Glucokinase, Glucose Homeostasis, and Diabetes Mellitus

Overview

Journal Curr Diab Rep

Publisher Current Science

Specialty Endocrinology

Date 2005 Jun 3

PMID 15929862

Citations 55

Authors

Franz M Matschinsky

Affiliations

Soon will be listed here.

Abstract

The enzyme glucokinase (GK) regulates the rate of glucose metabolism in many tissues, including liver, the pancreatic b cells, certain neurons, enteroendocrine cells, and the pituitary, serving as a glucose sensor in many of these. Thus, GK plays a critical role in glucose homeostasis. Spontaneous mutants of GK in humans result in autosomal-dominant hypo- and hyperglycemia syndromes described as "GK disease." GK activator drugs have been discovered that lower blood glucose in normal and diabetic animals and promise to be useful in the treatment of type 2 diabetes mellitus. There is no question that the GK molecule and related issues will continue to be a fruitful topic for future research.

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References

Christesen H, Jacobsen B, Odili S, Buettger C, Cuesta-Munoz A, Hansen T . The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy. Diabetes. 2002; 51(4):1240-6. DOI: 10.2337/diabetes.51.4.1240. View

Magnuson M . Glucokinase gene structure. Functional implications of molecular genetic studies. Diabetes. 1990; 39(5):523-7. DOI: 10.2337/diab.39.5.523. View

Gloyn A . Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy. Hum Mutat. 2003; 22(5):353-62. DOI: 10.1002/humu.10277. View

Gloyn A, Noordam K, Willemsen M, Ellard S, Lam W, Campbell I . Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations. Diabetes. 2003; 52(9):2433-40. DOI: 10.2337/diabetes.52.9.2433. View

Collins H, Najafi H, Buettger C, Rombeau J, Settle R, Matschinsky F . Identification of glucose response proteins in two biological models of beta-cell adaptation to chronic high glucose exposure. J Biol Chem. 1992; 267(2):1357-66. View

Iynedjian P, Pilot P, Nouspikel T, Milburn J, Quaade C, Hughes S . Differential expression and regulation of the glucokinase gene in liver and islets of Langerhans. Proc Natl Acad Sci U S A. 1989; 86(20):7838-42. PMC: 298166. DOI: 10.1073/pnas.86.20.7838. View

Vandercammen A, Detheux M, Van Schaftingen E . Binding of sorbitol 6-phosphate and of fructose 1-phosphate to the regulatory protein of liver glucokinase. Biochem J. 1992; 286 ( Pt 1):253-6. PMC: 1133047. DOI: 10.1042/bj2860253. View

Gloyn A, Odili S, Zelent D, Buettger C, Castleden H, Steele A . Insights into the structure and regulation of glucokinase from a novel mutation (V62M), which causes maturity-onset diabetes of the young. J Biol Chem. 2005; 280(14):14105-13. DOI: 10.1074/jbc.M413146200. View

Magnuson M, Shelton K . An alternate promoter in the glucokinase gene is active in the pancreatic beta cell. J Biol Chem. 1989; 264(27):15936-42. View

10.

Brocklehurst K, Payne V, Davies R, Carroll D, Vertigan H, Wightman H . Stimulation of hepatocyte glucose metabolism by novel small molecule glucokinase activators. Diabetes. 2004; 53(3):535-41. DOI: 10.2337/diabetes.53.3.535. View

11.

Grimsby J, Sarabu R, Corbett W, Haynes N, Bizzarro F, Coffey J . Allosteric activators of glucokinase: potential role in diabetes therapy. Science. 2003; 301(5631):370-3. DOI: 10.1126/science.1084073. View

12.

Kamata K, Mitsuya M, Nishimura T, Eiki J, Nagata Y . Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase. Structure. 2004; 12(3):429-38. DOI: 10.1016/j.str.2004.02.005. View

13.

Matschinsky F . Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes. 1996; 45(2):223-41. DOI: 10.2337/diab.45.2.223. View

14.

Bedoya F, Matschinsky F, Shimizu T, ONeil J, Appel M . Differential regulation of glucokinase activity in pancreatic islets and liver of the rat. J Biol Chem. 1986; 261(23):10760-4. View

15.

Toyoda Y, Yoshie S, Shironoguchi H, Miwa I . Glucokinase is concentrated in insulin-secretory granules of pancreatic B-cells. Histochem Cell Biol. 1999; 112(1):35-40. DOI: 10.1007/s004180050389. View

16.

Inoue M, Sakuraba Y, Motegi H, Kubota N, Toki H, Matsui J . A series of maturity onset diabetes of the young, type 2 (MODY2) mouse models generated by a large-scale ENU mutagenesis program. Hum Mol Genet. 2004; 13(11):1147-57. DOI: 10.1093/hmg/ddh133. View

17.

Glaser B, Kesavan P, Heyman M, Davis E, Cuesta A, Buchs A . Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med. 1998; 338(4):226-30. DOI: 10.1056/NEJM199801223380404. View

18.

Toyoda Y, Tsuchida A, Iwami E, Shironoguchi H, Miwa I . Regulation of hepatic glucose metabolism by translocation of glucokinase between the nucleus and the cytoplasm in hepatocytes. Horm Metab Res. 2001; 33(6):329-36. DOI: 10.1055/s-2001-15418. View

19.

Hughes S, Quaade C, Milburn J, Cassidy L, Newgard C . Expression of normal and novel glucokinase mRNAs in anterior pituitary and islet cells. J Biol Chem. 1991; 266(7):4521-30. View

20.

Liang Y, Najafi H, Matschinsky F . Glucose regulates glucokinase activity in cultured islets from rat pancreas. J Biol Chem. 1990; 265(28):16863-6. View