The genetic basis of congenital hyperinsulinism

Journal of Medical Genetics

Volumn 46, Issue 5, 2009, Pages 289-299

  James, C ^a   Kapoor, R R ^a   Ismail, D ^a   Hussain, K ^a,b  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYACYL COENZYME A DEHYDROGENASE; ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; DIAZOXIDE; GLIBENCLAMIDE; GLUCOKINASE; GLUTAMATE DEHYDROGENASE; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; INSULIN; MONOCARBOXYLATE TRANSPORTER 1; SULFONYLUREA RECEPTOR 1; TOLBUTAMIDE;

AUTOSOMAL DOMINANT INHERITANCE; AUTOSOMAL RECESSIVE INHERITANCE; BIOGENESIS; CELL FUNCTION; GENE MUTATION; GENETIC COUNSELING; GENETIC HETEROGENEITY; HETEROZYGOSITY; HUMAN; INFANT; INSULIN BLOOD LEVEL; INSULIN RELEASE; NEWBORN; NON INSULIN DEPENDENT DIABETES MELLITUS; NUCLEOTIDE SEQUENCE; PANCREAS ISLET BETA CELL; PANCREAS RESECTION; PATIENT CARE; PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA OF INFANCY; PRIORITY JOURNAL; REVIEW;

ATP-BINDING CASSETTE TRANSPORTERS; GENES, RECESSIVE; GENETIC HETEROGENEITY; GENETIC PREDISPOSITION TO DISEASE; HUMANS; INSULIN; INSULIN-SECRETING CELLS; MUTATION; PERSISTENT HYPERINSULINEMIA HYPOGLYCEMIA OF INFANCY; POTASSIUM CHANNELS, INWARDLY RECTIFYING; RECEPTORS, DRUG;

EID: 66249114971     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmg.2008.064337     Document Type: Review

References (138)

1. Stanley CA. Hyperinsulinism in infants and children. Pediatr Clin North Am 1997;44:363-74.
2. Hussain K, Blankenstein O, De Lonlay P, Christesen HT. Hyperinsulinaemic hypoglycaemia biochemical basis and the importance of maintaining normoglycaemia during management. Arch Dis Child 2007;92:568-70.
3. Bruninig GJ. Recent advances in hyperinsulinism and the pathogenesis of diabetes mellitus. Curr Opin Pediatr 1990;2:758- 65.
4. Fournet JC, Junien C. The genetics of neonatal hyperinsulinism. Horm Res 2003;59:30-4.
5. Glaser B, Thornton PS, Otonkoski T, Junien C. The genetics of neonatal hyperinsulinism. Arch Dis Child 2000;82:79-86.
6. de Lonlay P, Fournet JC, Touati G, Groos MS, Martin D, Sevin C, Delagne V, Mayaud C, Chigot V, Sempoux C, Brusset MC, Laborde K, Bellane-Chantelot C, Vassault A, Rahier J, Junien C, Brunelle F, Nihoul-Fékété C, Saudubray JM, Robert JJ. Heterogeneity of persistent hyperinsulinaemic hypoglycaemia. A series of 175 cases. Eur J Pediatr 2002;161:37-48.
7. Meissner T, Mayatepek E. Clinical and genetic heterogeneity in congenital hyperinsulinism. Eur J Pediatr 2002;161:6-20.
8. Sempoux C, Guiot Y, Lefevre A, Nihoul-Fekete C, Jaubert F, Saudubray JM, Rahier J. Neonatal hyperinsulinemic hypoglycemia: heterogeneity of the syndrome and keys for differential diagnosis. J Clin Endocrinol Metab 1998;83:1455-61.
9. Nestorowicz A, Glaser B, Wilson BA, Shyng SL, Nichols CG, Stanley CA, Thornton PS, Permutt MA. Genetic heterogeneity in familial hyperinsulinism. Hum Mol Genet 1998;7:1119-28.
10. Thomas P, Ye Y, Lightner E. Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy. Hum Mol Genet 1996;5:1809-12.
11. Thomas PM, Cote GJ, Wohllk N, Haddad B, Mathew PM, Rabl W, Aguilar-Bryan L, Gagel RF, Bryan J. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science 1995;268:426-9.
12. Nestorowicz A, Inagaki N, Gonoi T, Schoor KP, Wilson BA, Glaser B, Landau H, Stanley CA, Thornton PS, Seino S, Permutt MA. A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism. Diabetes 1997;46:1743-8.
13. Dunne MJ, Kane C, Shepherd RM, Sanchez JA, James RF, Johnson PR, Aynsley- Green A, Lu S, Clement JP IV, Lindley KJ, Seino S, Aguilar-Bryan L. Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor. N Engl J Med 1997;336:703-6.
14. Otonkoski T, Ammala C, Huopio H, Cote GJ, Chapman J, Cosgrove K, Ashfield R, Huang E, Komulainen J, Ashcroft FM, Dunne MJ, Kere J, Thomas PM. A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland. Diabetes 1999;48:408-15.
15. Tanizawa Y, Matsuda K, Matsuo M, Ohta Y, Ochi N, Adachi M, Koga M, Mizuno S, Kajita M, Tanaka Y, Tachibana K, Inoue H, Furukawa S, Amachi T, Ueda K, Oka Y. Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy: nucleotide-binding fold-2 mutation impairs cooperative binding of adenine nucleotides to sulfonylurea receptor 1. Diabetes 2000;49:114-20.
16. Marthinet E, Bloc A, Oka Y, Tanizawa Y, Wehrle-Haller B, Bancila V, Dubuis JM, Philippe J, Schwitzgebel VM. Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate- sensitive potassium channel impairing trafficking and function. J Clin Endocrinol Metab 2005;90:5401-6.
17. Tornovsky S, Crane A, Cosgrove KE, Hussain K, Lavie J, Heyman M, Nesher Y, Kuchinski N, Ben-Shushan E, Shatz O, Nahari E, Potikha T, Zangen D, Tenenbaum-Rakover Y, de Vries L, Argente J, Gracia R, Landau H, Eliakim A, Lindley K, Dunne MJ, Aguilar-Bryan L, Glaser B. Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity. J Clin Endocrinol Metab 2004;89:6224-34.
18. Ashcroft FM, Harrison DE, Ashcroft SJ. Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells. Nature 1984;312:446-8.
19. Clayton PT, Eaton S, Aynsley-Green A, Edginton M, Hussain K, Krywawych S, Datta V, Malingre HE, Berger R, van den Berg IE. Hyperinsulinism in short-chain L-3- hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Invest 2001;108:457-65.
20. Hussain K, Clayton PT, Krywawych S, Chatziandreou I, Mills P, Ginbey DW, Geboers AJ, Berger R, van den Berg IE, Eaton S. Hyperinsulinism of infancy associated with a novel splice site mutation in the SCHAD gene. J Pediatr 2005;146:706-8.
21. Molven A, Matre GE, Duran M, Wanders RJ, Rishaug U, Njolstad PR, Jellum E, Sovik O. Familial hyperinsulinaemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. Diabetes 2004;53:221-7.
22. Huopio H, Reimann F, Ashfield R, Komulainen J, Lenko HL, Rahier J, Vauhkonen I, Kere J, Laakso M, Ashcroft F, Otonkoski T. Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1. J Clin Invest 2000;106:897-906.
23. Thornton PS, MacMullen C, Ganguly A, Ruchelli E, Steinkrauss L, Crane A, Aguilar- Bryan L, Stanley CA. Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor. Diabetes 2003;52:2403-10.
24. Pinney SE, MacMullen C, Becker S, Lin YW, Hanna C, Thornton P, Ganguly A, Shyng SL, Stanley CA. Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. JClin Invest 2008;118:2877-86.
25. Lin YW, Macmullen C, Ganguly A, Stanley CA, Shyng SL. A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels. J Biol Chem 2006;281:3006-12.
26. Stanley CA, Lieu YK, Hsu BYL, Burlina AB, Greenberg CR, Hopwood NJ, Perlman K, Rich BH, Zammarchi E, Poncz M. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med 1998;338:1352-7.
27. Stanley CA, Fang J, Kutyna K, Hsu BY, Ming JE, Glaser B, Poncz M. Molecular basis and characterization of the hyperinsulinism/hyperammonemia syndrome: predominance of mutations in exons 11 and 12 of the glutamate dehydrogenase gene. Diabetes 2000;49:667-73.
28. Yorifuji T, Muroi J, Uematsu A, Hiramatsu H, Momoi T. Hyperinsulinism hyperammonemia syndrome caused by mutant glutamate dehydrogenase accompanied by novel enzyme kinetics. Hum Genet 1999;104:476-9.
29. Miki Y, Taki T, Ohura T, Kato H, Yanagisawa M, Hayashi Y. Novel missense mutations in the glutamate dehydrogenase gene in the congenital hyperinsulinism hyperammonemia syndrome. J Pediatr 2000;136:69-72.
30. Santer R, Kinner M, Passarge M, Superti-Furga A, Mayatepek E, Meissner T, Schneppenheim R, Schaub J. Novel missense mutations outside the allosteric domain of glutamate dehydrogenase are prevalent in European patients with the congenital hyperinsulinism-hyperammonemia syndrome. Hum Genet 2001;108:66-71.
31. Fujioka H, Okano Y, Inada H, Asada M, Kawamura T, Hase Y, Yamano T. Molecular characterisation of glutamate dehydrogenase gene defects in Japanese patients with congenital hyperinsulinism/hyperammonaemia. Eur J Hum Genet 2001;9:931-7.
32. Glaser B, Kesavan P, Heyman M, Davis E, Cuesta A, Buchs A, Stanley CA, Thornton PS, Permutt MA, Matschinsky FM, Herold KC. Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med 1998;338:226-30.
33. Christesen HB, Jacobsen BB, Odili S, Buettger C, Cuesta-Munoz A, Hansen T, Brusgaard K, Massa O, Magnuson MA, Shiota C, Matschinsky FM, Barbetti F. The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy. Diabetes 2002;51 :1240-6.
34. Gloyn AL, Noordam K, Willemsen MA, Ellard S, Lam WW, Campbell IW, Midgley P, Shiota C, Buettger C, Magnuson MA, Matschinsky FM, Hattersley AT. Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations. Diabetes 2003;52:2433- 40.
35. Cuesta-Munoz AL, Huopio H, Otonkoski T, Gomez-Zumaquero JM, Nanto-Salonen K, Rahier J, Lopez-Enriquez S, Garcia-Gimeno MA, Sanz P, Soriguer FC, Laakso M. Severe Persistent Hyperinsulinemic Hypoglycemia due to a De Novo Glucokinase Mutation. Diabetes 2004;53:2164-8.
36. Dullaart RP, Hoogenberg K, Rouwe CW, Stulp BK. Family with autosomal dominant hyperinsulinism associated with A456V mutation in the glucokinase gene. Journal of Internal Medicine 2004;255:143-5.
37. Wabitsch M, Lahr G, Van de Bunt M, Marchant C, Lindner M, von Puttkamer J, Fenneberg A, Debatin KM, Klein R, Ellard S, Clark A, Gloyn AL. Heterogeneityindisease severity in a family with a novel G68V GCK activating mutation causing persistent hyperinsulinaemic hypoglycaemia of infancy. Diabet Med 2007;24:1393-9.
38. Christesen HB, Tribble ND, Molven A, Siddiqui J, Sandal T, Brusgaard K, Ellard S, Njoølstad PR, Alm J, Brock Jacobsen B, Hussain K, Gloyn AL. 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;159:27-34.
39. Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, Ellard S, Ferrer J, Hattersley AT. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 2007;4:e118.
40. Fajans SS, Bell GI. Macrosomia and neonatal hypoglycaemia in RW pedigree subjects with a mutation (Q268X) in the gene encoding hepatocyte nuclear factor 4alpha (HNF4A). Diabetologia 2007;50:2600-1.
41. Kapoor R, Locke J, Colclough K, Wales J, Conn J, Ellard S, Hussain K. Persistent Hyperinsulinaemic Hypoglycaemia and Maturity Onset Diabetes of the Young (MODY) due to Heterozygous HNF4A Mutations. Diabetes 2008;57:1659-63.
42. Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, Parton LE, Schuit F, Quintens R, Sipila I, Mayatepek E, Meissner T, Halestrap AP, Rutter GA, KereJ. Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells. Am J Hum Genet 2007;81:467-74.
43. Fournet JC, Junien C. Genetics of congenital hyperinsulinism. Endocr Pathol 2004;15:233-40.
44. Someya T, Miki T, Sugihara S, Minagawa M, Yasuda T, Kohno Y, Seino S. Characterization of genes encoding the pancreatic p-cell ATP-sensitive K+ channel in persistent hyperinsulinemic hypoglycemia of infancy in Japanese patients. Endocr J 2000;47:715-22.
45. Rahier J, Guiot Y, Sempoux C. Persistent hyperinsulinaemic hypoglycaemia of infancy: a heterogeneous syndrome unrelated to nesidioblastosis. Arch Dis Child Fetal Neonatal Ed 2002;82:F108- 12.
46. Hussain K, Flanagan SE, Smith VV, Ashworth M, Day M, Pierro A, Ellard S. An ABCC8 gene mutation and mosaic uniparental isodisomy resulting in atypical diffuse congenital hyperinsulinism. Diabetes 2008;57:259-63.
47. Kapoor R, James C, Hussain K. Advances in the diagnosis and management of hyperinsulinaemic hypoglycaemia. Nat Clin Pract Endocrinol Metab 2009;5:101-12.
48. Peranteau WH, Ganguly A, Steinmuller L, Thornton P, Johnson MP, Howell LJ, Stanley CA, Adzick NS. Prenatal diagnosis and postnatal management of diffuse congenital hyperinsulinism: a case report. Fetal Diagn Ther 2006;21:515-8.
49. Seino S, Miki T. Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog Biophys Mol Biol 2003;81:133-76.
50. Ashcroft FM. ATP-sensitive potassium channelopathies: focus on insulin secretion. J Clin Invest 2005;115:2047-58.
51. Ashcroft FM. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci 1988;11:97-118.
52. Inagaki N, Gonoi T, Clement JP 4th, Namba N, Inazawa J, Gonzalez G, Aguilar- Bryan L, Seino S, Bryan J. Reconstitution of KATP: An inward rectifier subunit plus the sulphonylurea receptor. Science 1995;270:1166-70.
53. Tucker SJ, Gribble FM, Proks P, Trapp S, Ryder TJ, Haug T, Reimann F, Ashcroft FM. Molecular determinants of K-ATP channel inhibition by ATP. EMBO J 1998;17:3290-6.
54. Aguilar-Bryan L, Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev 1999;20:101-35.
55. Heron L, Virsolvy A, Peyrollier K, Gribble FM, Le Cam A, Ashcroft FM, Bataille D. Human a-endosulfine, a possible regulator of sulfonylurea-sensitive KATP channel: Molecular cloning, expression and biological properties. Proc Natl Acad Sci 1998;95:8387-91.
56. Conti LR, Radeke CM, Shyng SL, Vandenberg CA. Transmembrane topology of the sulfonylurea receptor SUR1. J Biol Chem 2001;276:41270-8.
57. Ueda K, Komine J, Matsuo M, Seino S, Amachi T. Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide. Proc Natl Acad Sci USA 1999;96:1268-72.
58. Matsuo M, Kimura Y, Ueda K. KATP channel interaction with adenine nucleotides. J Mol Cell Cardiol 2005;38:907-16.
59. Zerangue N, Schwappach B, Jan YN, Jan LY. A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron 1999;22:537-48.
60. Tucker SJ, Gribble FM, Zhao C, Trapp S, Ashcroft FM. Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor. Nature 1997;387:179-83.
61. Sharma N, Crane A, Clement JPt, Gonzalez G, Babenko AP, Bryan J, Aguilar-Bryan L. The C terminus of SUR1 is required for trafficking of KATP channels. J Biol Chem 1999;274:20628-32.
62. Babenko AP, Aguilar-Bryan L, Bryan J. A view of sur/KIR6.X, KATP channels. Annu Rev Physiol 1998;60:667-87.
63. Clement JP 4th, Kunjilwar K, Gonzalez G, Schwanstecher M, Panten U, Aguilar- Bryan L, Bryan J. Association and stoichiometry of K(ATP) channel subunits. Neuron 1997;18:827-38.
64. Aguilar-Bryan L, Clement JP IV, Gonzalez G, Kunjilwar K, Babenko A, Bryan J. Toward understanding the assembly and structure of KATP channels. Physiol Rev 1998;78:227-45.
65. Inagaki N, Gonoi T, Clement JP, Wang CZ, Aguilar-Bryan L, Bryan J, Seino S. A family of sulfonylurea receptors determines the pharmacological properties of ATP- sensitive K+ channels. Neuron 1996;16:1011-17.
66. Aguilar-Bryan L, Nichols GC, Wechsler WS, Clement JP IV, Boyd AE III, Gonzalez G, Herrers-Sosa E, Nguy K, Bryan J, Nelson DA. Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science 1995;268:423-6.
67. Bitner-Glindzicz M, Lindley KJ, Rutland P, Blaydon D, Smith VV, Milla PJ, Hussain K, Furth-Lavi J, Cosgrove KE, Shepherd RM, Barnes PD, O'Brien RE, Farndon PA, Sowden J, Liu XZ, Scanlon MJ, Malcolm S, Dunne MJ, Aynsley-Green A, Glaser B. A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher Type 1C gene. Nat Gene 2000;26:56-60.
68. Fernández-Marmiesse A, Salas A, Vega A, Fernández-Lorenzo JR, Barreiro J, Carracedo A. Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of Infancy (HI). Hum Mutat 2006;27:214.
69. Flanagan SE, Clauin S, Bellanné-Chantelot C, de Lonlay P, Harries LW, Gloyn AL, Ellard S. Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat 2009;30:170-80.
70. Dekel B, Lubin D, Modan-Moses D, Quint J, Glaser B, Meyerovitch J. Compound heterozygosity for the common sulfonylurea receptor mutations can cause mild diazoxide-sensitive hyperinsulinism. Clin Pediatr (Phila) 2002;41:183-6.
71. Muzyamba M, Farzaneh T, Behe P, Thomas A, Christesen HB, Brusgaard K, Hussain K, Tinker A. Complex ABCC8 DNA variations in congenital hyperinsulinism: lessons from functional studies. Clin Endocrinol (Oxf) 2007;67:115-24.
72. Crane A, Aguilar-Bryan L. Assembly, maturation, and turnover of K(ATP) channel subunits. J Biol Chem 2004;279:9080-90.
73. Cartier EA, Conti LR, Vandenberg CA, Shyng SL. Defective trafficking and function of KATP channels caused by a sulfonylurea receptor 1 mutation associated with persistent hyperinsulinemic hypoglycemia of infancy. Proc Natl Acad Sci USA 2001;98:2882-7.
74. Partridge CJ, Beech DJ, Sivaprasadarao A. Identification and pharmacological correction of a membrane trafficking defect associated with a mutation in the sulfonylurea receptor causing familial hyperinsulinism. J Biol Chem 2001;276:35947-52.
75. Shyng SL, Ferrigni T, Shepard JB, Nestorowicz A, Glaser B, Permutt MA, Nichols CG. Functional analyses of novel mutations in the sulfonylurea receptor 1 associated with persistent hyperinsulinemic hypoglycemia of infancy. Diabetes 1998;47:1145-51.
76. Taschenberger G, Mougey A, Shen S, Lester LB, LaFranchi S, Shyng SL. Identification of a familial hyperinsulinism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels. J Biol Chem 2002;277:7139-16.
77. Matsuo M, Trapp S, Tanizawa Y, Kioka N, Amachi T, Oka Y, Ashcroft FM, Ueda K. Functional analysis of a mutant sulfonylurea receptor, SUR1-R1420C, thatis responsible for persistent hyperinsulinemic hypoglycemia of infancy. J Biol Chem 2000;275:41184-91.
78. Nichols CG, Shyng SL, Nestorowicz A, Glaser B, Clement JP 4th, Gonzalez G, Aguilar-Bryan L, Permutt MA, Bryan J. Adenosine diphosphate as an intracellular regulator of insulin secretion. Science 1996;272:1785-7.
79. Branstrom R, Leibiger IB, Leibiger B, Corkey BE, Berggren PO, Larsson 0. Long chain coenzyme A esters activate the pore-forming subunit (Kir6. 2) of the ATP- regulated potassium channel. J Biol Chem 1998;273:31395-400.
80. Deloukas P, Dauwerse JG, Moschonas NK, van Ommen GJ, van Loon AP. Three human glutamate dehydrogenase genes (GLUD1, GLUDP2, and GLUDP3) are located on chromosome 10q, but are not closely physically linked. Genomics 1993;17:676-81.
81. Hudson RC, Daniel RM. L-glutamate dehydrogenases: distribution, properties and mechanism. Comp Biochem Physiol B 1993;106:767-92.
82. Kelly A, Li C, Gao Z, Stanley CA, Matschinsky FM. Glutaminolysis and Insulin Secretion: From Bedside to Bench and Back. Diabetes 2002;51:S421-6.
83. Fahien LA, MacDonald MJ, Kmiotek EH, Mertz RJ, Fahien CM. Regulation of insulin release by factors that also modify glutamate dehydrogenase. J Biol Chem 1980;263:13610-14.
84. Weinzimer SA, Stanley CA, Berry GT, Yudkoff M, Tuchman M, Thornton PS. A syndrome of congenital hyperinsulinism and hyperammonemia. J Pediatr 1997;130:661-4.
85. Zammarchi E, Filippi L, Novembre E, Donati MA. Biochemical evaluation of a patient with a familial form of leucine-sensitive hypoglycemia and concomitant hyperammonemia. Metabolism 1996;45:957-60.
86. Stanley CA. Hyperinsulinism/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism. Mol Genet Metab 2004;81 :S45-51.
87. Raizen DM, Brooks-Kayal A, Steinkrauss L, Tennekoon GI, Stanley CA, Kelly A. Central nervous system hyperexcitability associated with glutamate dehydrogenase gain of function mutations. J Pediatr 2005;146:388- 94.
88. MacMullen C, Fang J, Hsu BY, Kelly A, de Lonlay-Debeney P, Saudubray JM, Ganguly A, Smith TJ, Stanley CA, Hyperinsulinism/hyperammonemia Contributing Investigators. Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase. J Clin Endocrinol Metab 2001;86:1782-7.
89. lynedjian PB, Md'bius G, Seitz HJ, Wollheim CB, Renold AE. Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets. Proc Natl Acad Sci USA 1986;83:1998- 2001.
90. Matschinsky FM. Regulation of pancreatic beta-cell glucokinase: from basics to therapeutics. Diabetes 2002;51:S394-404.
91. Zelent D, Najafi H, Odili S, Buettger C, Weik-Collins H, Li C, Doliba N, Grimsby J, Matschinsky FM. Glucokinase and glucose homeostasis: proven concepts and new ideas. Biochem Soc Trans 2005;33:306-10.
92. Ralph EC, Thomson J, Almaden J, Sun S. Glucose modulation of glucokinase activation by small molecules. Biochemistry 2008;47:5028-36.
93. Heredia VV, Carlson TJ, Garcia E, Sun S. Biochemical basis of glucokinase activation and the regulation by glucokinase regulatory protein in naturally occurring mutations. J Biol Chem 2006;281:40201-7.
94. Van de Bunt M, Edghill ML, Hussain K, Ellard S, Gloyn A. Gene duplications resulting in over expression of glucokinase are not a common cause of hypoglycaemia of infancy in humans. Mol Genet Metab 2008;94:268-9.
95. Christesen HB, 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;68:1011.
96. Vredendaal PJ, van den Berg IE, Malingree HE, Stroobants AK, Olde Weghuis DE, Berger Human short-chain L-3-hydroxyacyl-CoA dehydrogenase: cloning and characterization of the coding sequence. Biochem Biophys Res Commun 1996;223:718-23.
97. Vredendaal PJ, van den Berg IE, Stroobants AK, van der ADL, Malingré HE, Berger R. Structural organization of the human short-chain L-3-hydroxyacyl-CoA dehydrogenase gene. Mamm Genome 1998;9:763-8.
98. Hardy OT, Hohmeier HE, Becker TC, Manduchi E, Doliba NM, Gupta RK, White P, Stoeckert CJ Jr, Matschinsky FM, Newgard CB, Kaestner KH. Functional genomics of the beta-cell: short-chain 3-hydroxyacyl-coenzyme A dehydrogenase regulates insulin secretion independent of K+ currents. Mol Endocrinol 2007;21:765-73.
99. Martens GA, Vervoort A, Van de Casteele M, Stangé G, Hellemans K, Van Thi HV, Schuit F, Pipeleers D. Specificity in beta cell expression of L-3-hydroxyacyl-CoA dehydrogenase, short chain, and potential role in down-regulating insulin release. J Biol Chem 2007;282:21134- 44.
100. Lantz KA, Vatamaniuk MZ, Brestelli JE, Friedman JR, Matschinsky FM, Kaestner KH. Foxa2 regulates multiple pathways of insulin secretion. J Clin Invest 2004;14:512-20.
101. Sund NJ, Vatamaniuk MZ, Casey M, Ang SL, Magnuson MA, Stoffers DA, Matschinsky FM, Kaestner KH. Tissue-specific deletion of Foxa2 in pancreatic beta cells results in hyperinsulinemic hypoglycemia. Genes Dev 2001;15:1706-15.
102. Meissner T, Otonkoski T, Feneberg R, Beinbrech B, Apostolidou S, Sipilä I, Schaefer F, Mayatepek E. Exercise induced hypoglycaemic hyperinsulinism. Arch Dis Child 2001;84:254-7.
103. Meissner T, Friedmann B, Okun JG, Schwab MA, Otonkoski T, Bauer T, Baartsch P, Mayatepek E. Massive insulin secretion in response to anaerobic exercise in exercise-induced hyperinsulinism. Horm Metab Res 2005;37:690-4.
104. Halestrap AP, Price NT. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J 1999;343:281-99.
105. Cuff MA, Shirazi-Beechey SP. The human monocarboxylate transporter, MCT1: genomic organization and promoter analysis. Biochem Biophys Res Commun 2002;292:1048-56.
106. Garcia CK, Li X, Luna J, Francke U. cDNA cloning of the human monocarboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12. Genomics 1994;23:500-3.
107. Zhao C, Rutter GA. Overexpression of lactate dehydrogenase A attenuates glucose- induced insulin secretion in stable MIN-6 beta-cell lines. FEBS Lett 1998;430:213-6.
108. Ishihara H, Wang H, Drewes LR, Wollheim CB. Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells. J Clin Invest 1999;104:1621-9.
109. Otonkoski T, Kaminen N, Ustinov J, Lapatto R, Meissner T, Mayatepek E, Kere J, Sipilaa I. Physical exercise-induced hyperinsulinemic hypoglycemia is an autosomal- dominant trait characterized by abnormal pyruvate-induced insulin release. Diabetes 2003;52(1):199-204.
110. Duncan SA, Navas MA, Dufort D, et al. Regulation of a transcription factor network required for differentiation and metabolism. Science 1998;281:692-5.
111. Sladek FM, Zhong WM, Lai E, Darnell JE Jr. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev 1990;4(12B):2353-65.
112. Boj SF, Parrizas M, Maestro MA, Ferrer J. A transcription factor regulatory circuit in differentiated pancreatic cells. Proc Natl Acad Sci USA 2001;98:14481-6.
113. Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, Volkert TL, Schreiber J, Rolfe PA, Gifford DK, Fraenkel E, Bell GI, Young RA. Control of pancreas and liver gene expression by HNF transcription factors. Science 2004;303:1378-81.
114. Wang H, Maechler P, Antinozzi PA, Hagenfeldt KA, Wollheim CB. Hepatocyte nuclear factor 4alpha regulates the expression of pancreatic beta-cell genes implicated in glucose metabolism and nutrient-induced insulin secretion. J Biol Chem 2000;275:35953-9.
115. Hadzopoulou-Cladaras M, Kistanova E, Evagelopoulou C, Zeng S, Cladaras C, Ladias JAA. Functional domains of the nuclear receptor hepatocyte nuclear factor 4. J Biol Chem 1997;272:539-50.
116. Thomas H, Jaschkowitz K, Bulman M, Frayling TM, Mitchell SM, Roosen S, Lingott- Frieg A, Tack CJ, Ellard S, Ryffel GU, Hattersley AT. A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum Mol Genet 2001;10:2089-97.
117. Yamagata K, Furuta H, Oda N, Kaisaki P, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell GI. Mutations in the hepatocyte nuclear factor-4alpha genein maturity-onset diabetes of the young (MODY1). Nature 1996;384:458-60.
118. Stoffel M, Duncan SA. The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci USA 1997;94:13209-14.
119. Gupta RK, Vatamaniuk MZ, Lee CS, Flaschen RC, Fulmer JT, Matschinsky FM, Duncan SA, Kaestner KH. The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. J Clin Invest 2005;115:1006-15.
120. Miura A, Yamagata K, Kakei M, Hatakeyama H, Takahashi N, Fukui K, Nammo T, Yoneda K, Inoue Y, Sladek FM, Magnuson MA, Kasai H, Miyagawa J, Gonzalez FJ, Shimomura I. Hepatocyte nuclear factor-4alpha is essential for glucose-stimulated insulin secretion by pancreatic beta-cells. J Biol Chem 2006;281 :5246-57.
121. Rahier J, Guiot Y, Sempoux C. Persistent hyperinsulinaemic hypoglycaemia of infancy: a heterogeneous syndrome unrelated to nesidioblastosis. Arch Dis Child Fetal Neonatal Ed 2000;82:F108- 12.
122. Goossens A, Gepts W, Saudubray JM, Bonnefont JP, Nihoul-Fekete, Heitz PU, Kloppel G. Diffuse and focal nesidioblastosis. A clinicopathological studyof24 patients with persistent neonatal hyperinsulinemic hypoglycemia. Am J Surg Pathol 1989;13:766-75.
123. Verkarre V, Fournet JC, de Lonlay P, Gross-Morand MS, Devillers M, Rahier J, Brunelle F, Robert JJ, Nihoul-Fekete C, Saudubray JM, Junien C. Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia. J Clin Invest 1998;102:1286-91.
124. de Lonlay P, Fournet JC, Rahier J, Gross-Morand MS, Poggi-Travert F, Foussier V, Bonnefont JP, Brusset MC, Brunelle F, Robert JJ, Nihoul-Fekete C, Saudubray JM, Junien C. Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy. J Clin Invest 1997;100:802-7.
125. Glaser B, Ryan F, Donath M, Landau H, Stanley CA, Baker L, Barton DE, Thornton PS. Hyperinsulinism caused by paternal-specific inheritance of a recessive mutation in the sulfonylurea-receptor gene. Diabetes 1999;48:1652-7.
126. Ryan F, Devaney D, Joyce C, Nestorowicz A, Permutt MA, Glaser B, Barton DE, Thornton PS. Hyperinsulinism: molecular aetiology of focal disease. Arch Dis Child 1998;79:445-7.
127. Fournet JC, Mayaud C, de Lonlay P, Gross-Morand MS, Verkarre V, Castanet M, Devillers M, Rahier J, Brunelle F, Robert JJ, Nihoul-Fekete C, Saudubray JM, Junien C. Unbalanced expression of 11p15 imprinted genes in focal forms of congenital hyperinsulinism: association with a reduction to homozygosity of a mutation in ABCC8 or KCNJ11. Am J Pathol 2001;158:2177-84.
128. Fournet JC, Mayaud C, de Lonlay P, Verkarre V, Rahier J, Brunelle F, Robert JJ, Nihoul-Fekete C, Saudubray JM, Junien C. Loss of imprinted genes and paternal SUR1 mutations lead to focal form of congenital hyperinsulinism. Horm Res 2000;53:2-6.
129. Damaj L, le Lorch M, Verkarre V, Werl C, Hubert L, Nihoul-Fékété C, Aigrain Y, de Keyzer Y, Romana SP, Bellanne-Chantelot C, de Lonlay P, Jaubert F. Chromosome 11p15 Paternal Isodisomy in Focal Forms of Neonatal Hyperinsulinism. J Clin Endocrinol Metab 2008;93:4941-17.
130. Giannoukakis N, Deal C, Paquette J, Goodyer C, Polychronakos C. Parental genomic imprinting of the human IGF2 gene. Nat Genet 1993;4:98-101.
131. Lee MP, Hu R-J, Johnson LA, Feinberg AP. Human KVLQT1 gene shows tissue- specific imprinting and encompasses Beckwith-Wiedemann syndrome chromosomal rearrangements. Nat Genet 1997;15:181-5.
132. Matsuoka S, Edwards M, Bai C, Parker S, Zhang P, Baldini A, Harper J, Elledge S. p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev 1995;9:650-62.
133. Zhang Y, Tycko B. Monoallelic expression of the human H19 gene. Nat Genet 1992;1 :40-4.
134. Hao Y, Crenshaw T, Moulton T, Newcomb E, Tycko B. Tumour-suppressor activity of H19 RNA. Nature 1993;365:764-7.
135. Hatada I, Inazawa J, Abe T, Nakayama M, Kaneko Y, Jinno Y, Niikawa N, Ohashi S, Fukushima Y, Iida K, Yutani C, Takahashi S, Chiba Y, Ohishi S, Mukai T. Genomic imprinting of human p57KIP2 and its reduced expression in Wilms' tumors. Hum Mol Genet 1996;5:783-8.
136. Guillemot F, Caspary T, Tilghman SM, Copeland NG, Gilbert DJ, Jenkins NA, Anderson DJ, Joyner AL, Rossant J, Nagy A. Genomic imprinting of Mash2, a mouse gene required for trophoblast development. Nat Genet 1995;9:235-42.
137. Giurgea I, Sempoux C, Bellanné-Chantelot C, Ribeiro M, Hubert L, Boddaert N, Saudubray JM, Robert JJ, Brunelle F, Rahier J, Jaubert F, Nihoul-Fékété C, de Lonlay P. The Knudson's two-hit model and timing of somatic mutation may account for the phenotypic diversity of focal congenital hyperinsulinism. J Clin Endocrinol Metab 2006;91:4118- 23.
138. Chik KK, Chan CW, Lam CW, Ng KL. Hyperinsulinism and hyperammonaemia syndrome due to a novel missense mutation in the allosteric domain of the Glutamate dehydrogenase 1 gene. J Paediatr Child Health 2008;44:517-9.