Mutations in Pancreatic ß-cell Glucokinase As a Cause of Hyperinsulinaemic Hypoglycaemia and Neonatal Diabetes Mellitus

Overview

Journal Rev Endocr Metab Disord

Publisher Springer

Specialty Endocrinology

Date 2010 Sep 30

PMID 20878480

Citations 12

Authors

Khalid Hussain

Affiliations

Soon will be listed here.

Abstract

Glucokinase is a key enzyme involved in regulating insulin secretion from the pancreatic ß-cell. The unique role of glucokinase in human glucose physiology is illustrated by the fact that genetic mutations in glucokinase can either cause hyperglycaemia or hypoglycaemia. Heterozygous inactivating mutations in glucokinase cause maturity-onset diabetes of the young (MODY), homozygous inactivating in glucokinase mutations result in permanent neonatal diabetes whereas heterozygous activating glucokinase mutations cause hyperinsulinaemic hypoglycaemia.

Citing Articles

Targeting Protein Kinases to Protect Beta-Cell Function and Survival in Diabetes.

Dalle S Int J Mol Sci. 2024; 25(12).

PMID: 38928130 PMC: 11203834. DOI: 10.3390/ijms25126425.

New-Generation Glucokinase Activators: Potential Game-Changers in Type 2 Diabetes Treatment.

Haddad D, Dsouza V, Al-Mulla F, Madhoun A Int J Mol Sci. 2024; 25(1).

PMID: 38203742 PMC: 10779250. DOI: 10.3390/ijms25010571.

Potential Therapeutic Targets for the Management of Diabetes Mellitus Type 2.

Prabhakar P, El-Saber Batiha G Curr Med Chem. 2023; 31(21):3167-3181.

PMID: 37125833 DOI: 10.2174/0929867330666230501172557.

Glucokinase Inhibition: A Novel Treatment for Diabetes?.

Remedi M, Nichols C Diabetes. 2023; 72(2):170-174.

PMID: 36669001 PMC: 9871191. DOI: 10.2337/db22-0731.

A new compound heterozygosis for inactivating mutations in the glucokinase gene as cause of permanent neonatal diabetes mellitus (PNDM) in double-first cousins.

Esquiaveto-Aun A, de Mello M, Paulino M, Minicucci W, Guerra-Junior G, de Lemos-Marini S Diabetol Metab Syndr. 2015; 7:101.

PMID: 26587058 PMC: 4652399. DOI: 10.1186/s13098-015-0101-9.

References

Pal P, Miller B . Activating mutations in the human glucokinase gene revealed by genetic selection. Biochemistry. 2009; 48(5):814-6. DOI: 10.1021/bi802142q. View

Dullaart R, Hoogenberg K, Rouwe C, Stulp B . Family with autosomal dominant hyperinsulinism associated with A456V mutation in the glucokinase gene. J Intern Med. 2003; 255(1):143-5. DOI: 10.1046/j.0954-6820.2003.01243.x. View

Rubio-Cabezas O, Diaz Gonzalez F, Aragones A, Argente J, Campos-Barros A . Permanent neonatal diabetes caused by a homozygous nonsense mutation in the glucokinase gene. Pediatr Diabetes. 2008; 9(3 Pt 1):245-9. DOI: 10.1111/j.1399-5448.2007.00361.x. View

Vaxillaire M, Samson C, Cave H, Metz C, Froguel P, Polak M . Glucokinase gene mutations are not a common cause of permanent neonatal diabetes in France. Diabetologia. 2002; 45(3):454-5. DOI: 10.1007/s00125-001-0741-1. View

Barbetti F, Cobo-Vuilleumier N, Dionisi-Vici C, Toni S, Ciampalini P, Massa O . Opposite clinical phenotypes of glucokinase disease: Description of a novel activating mutation and contiguous inactivating mutations in human glucokinase (GCK) gene. Mol Endocrinol. 2009; 23(12):1983-9. PMC: 5419125. DOI: 10.1210/me.2009-0094. View

Sayed S, Langdon D, Odili S, Chen P, Buettger C, Schiffman A . Extremes of clinical and enzymatic phenotypes in children with hyperinsulinism caused by glucokinase activating mutations. Diabetes. 2009; 58(6):1419-27. PMC: 2682682. DOI: 10.2337/db08-1792. View

Fernandez-Mejia C, Rodriguez-Dorantes M, Matschinsky F, Wang J, German M . Cyclic adenosine 3',5'-monophosphate increases pancreatic glucokinase activity and gene expression. Endocrinology. 2001; 142(4):1448-52. DOI: 10.1210/endo.142.4.8100. View

Cuesta-Munoz A, Huopio H, Otonkoski T, Gomez-Zumaquero J, Nanto-Salonen K, Rahier J . Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation. Diabetes. 2004; 53(8):2164-8. DOI: 10.2337/diabetes.53.8.2164. View

Middleton R . Hexokinases and glucokinases. Biochem Soc Trans. 1990; 18(2):180-3. DOI: 10.1042/bst0180180. View

10.

Turkkahraman D, Bircan I, Tribble N, Akcurin S, Ellard S, Gloyn A . Permanent neonatal diabetes mellitus caused by a novel homozygous (T168A) glucokinase (GCK) mutation: initial response to oral sulphonylurea therapy. J Pediatr. 2008; 153(1):122-6. DOI: 10.1016/j.jpeds.2007.12.037. View

11.

Grupe A, Hultgren B, Ryan A, Ma Y, Bauer M, Stewart T . Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis. Cell. 1995; 83(1):69-78. DOI: 10.1016/0092-8674(95)90235-x. View

12.

Christesen H, Tribble N, Molven A, Siddiqui J, Sandal T, Brusgaard K . Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation. Eur J Endocrinol. 2008; 159(1):27-34. DOI: 10.1530/EJE-08-0203. View

13.

Kassem S, Bhandari S, Rodriguez-Bada P, Motaghedi R, Heyman M, Garcia-Gimeno M . Large islets, beta-cell proliferation, and a glucokinase mutation. N Engl J Med. 2010; 362(14):1348-50. DOI: 10.1056/NEJMc0909845. View

14.

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

15.

Iynedjian P . Mammalian glucokinase and its gene. Biochem J. 1993; 293 ( Pt 1):1-13. PMC: 1134312. DOI: 10.1042/bj2930001. View

16.

Iynedjian P . Molecular physiology of mammalian glucokinase. Cell Mol Life Sci. 2008; 66(1):27-42. PMC: 2780631. DOI: 10.1007/s00018-008-8322-9. View

17.

Liang Y, Jetton T, ZIMMERMAN E, Najafi H, Matschinsky F, Magnuson M . Effects of alternate RNA splicing on glucokinase isoform activities in the pancreatic islet, liver, and pituitary. J Biol Chem. 1991; 266(11):6999-7007. View

18.

Matschinsky F . Regulation of pancreatic beta-cell glucokinase: from basics to therapeutics. Diabetes. 2002; 51 Suppl 3:S394-404. DOI: 10.2337/diabetes.51.2007.s394. View

19.

Christesen H, Brusgaard K, Beck Nielsen H, Brock Jacobsen B . Non-insulinoma persistent hyperinsulinaemic hypoglycaemia caused by an activating glucokinase mutation: hypoglycaemia unawareness and attacks. Clin Endocrinol (Oxf). 2008; 68(5):747-55. DOI: 10.1111/j.1365-2265.2008.03184.x. View

20.

Bennett K, James C, Mutair A, Al-Shaikh H, Sinani A, Hussain K . Four novel cases of permanent neonatal diabetes mellitus caused by homozygous mutations in the glucokinase gene. Pediatr Diabetes. 2011; 12(3 Pt 1):192-6. DOI: 10.1111/j.1399-5448.2010.00683.x. View