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Archives of Disease in Childhood. Fetal and Neonatal Edition logoLink to Archives of Disease in Childhood. Fetal and Neonatal Edition
. 2000 Mar;82(2):F87–F97. doi: 10.1136/fn.82.2.F87

Hyperinsulinism of infancy: towards an understanding of unregulated insulin release

R Shepherd, K Cosgrove, R O'Brien, P Barnes, C Ammala, M Dunne
PMCID: PMC1721057  PMID: 10685980

Abstract

Insulin is synthesised, stored, and secreted from pancreatic β cells. These are located within the islets of Langerhans, which are distributed throughout the pancreas. Less than 2% of the total pancreas is devoted to an endocrine function. When the mechanisms that control insulin release are compromised, potentially lethal diseases such as diabetes and neonatal hypoglycaemia are manifest. This article reviews the physiology of insulin release and illustrates how defects in these processes will result in the pathophysiology of hyperinsulinism of infancy.



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Selected References

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  1. Aguilar-Bryan L., Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev. 1999 Apr;20(2):101–135. doi: 10.1210/edrv.20.2.0361. [DOI] [PubMed] [Google Scholar]
  2. Aguilar-Bryan L., Clement J. P., 4th, Gonzalez G., Kunjilwar K., Babenko A., Bryan J. Toward understanding the assembly and structure of KATP channels. Physiol Rev. 1998 Jan;78(1):227–245. doi: 10.1152/physrev.1998.78.1.227. [DOI] [PubMed] [Google Scholar]
  3. Aguilar-Bryan L., Nichols C. G., Wechsler S. W., Clement J. P., 4th, Boyd A. E., 3rd, González G., Herrera-Sosa H., Nguy K., Bryan J., Nelson D. A. Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science. 1995 Apr 21;268(5209):423–426. doi: 10.1126/science.7716547. [DOI] [PubMed] [Google Scholar]
  4. Aizawa T., Komatsu M., Asanuma N., Sato Y., Sharp G. W. Glucose action 'beyond ionic events' in the pancreatic beta cell. Trends Pharmacol Sci. 1998 Dec;19(12):496–499. doi: 10.1016/s0165-6147(98)01273-5. [DOI] [PubMed] [Google Scholar]
  5. Ammälä C., Larsson O., Berggren P. O., Bokvist K., Juntti-Berggren L., Kindmark H., Rorsman P. Inositol trisphosphate-dependent periodic activation of a Ca(2+)-activated K+ conductance in glucose-stimulated pancreatic beta-cells. Nature. 1991 Oct 31;353(6347):849–852. doi: 10.1038/353849a0. [DOI] [PubMed] [Google Scholar]
  6. Ashcroft F. M., Gribble F. M. Correlating structure and function in ATP-sensitive K+ channels. Trends Neurosci. 1998 Jul;21(7):288–294. doi: 10.1016/s0166-2236(98)01225-9. [DOI] [PubMed] [Google Scholar]
  7. Ashcroft S. J., Ashcroft F. M. The sulfonylurea receptor. Biochim Biophys Acta. 1992 Dec 15;1175(1):45–59. doi: 10.1016/0167-4889(92)90008-y. [DOI] [PubMed] [Google Scholar]
  8. Ashfield R., Gribble F. M., Ashcroft S. J., Ashcroft F. M. Identification of the high-affinity tolbutamide site on the SUR1 subunit of the K(ATP) channel. Diabetes. 1999 Jun;48(6):1341–1347. doi: 10.2337/diabetes.48.6.1341. [DOI] [PubMed] [Google Scholar]
  9. Aspinwall C. A., Lakey J. R., Kennedy R. T. Insulin-stimulated insulin secretion in single pancreatic beta cells. J Biol Chem. 1999 Mar 5;274(10):6360–6365. doi: 10.1074/jbc.274.10.6360. [DOI] [PubMed] [Google Scholar]
  10. Aynsley-Green A., Dunne M. J., James R. F., Lindley K. J. Ions and genes in persistent hyperinsulinaemic hypoglycaemia in infancy: a commentary on the implications for tailoring treatment to disease pathogenesis. J Pediatr Endocrinol Metab. 1998 Mar;11 (Suppl 1):121–129. doi: 10.1515/jpem.1998.11.s1.121. [DOI] [PubMed] [Google Scholar]
  11. Aynsley-Green A., Polak J. M., Bloom S. R., Gough M. H., Keeling J., Ashcroft S. J., Turner R. C., Baum J. D. Nesidioblastosis of the pancreas: definition of the syndrome and the management of the severe neonatal hyperinsulinaemic hypoglycaemia. Arch Dis Child. 1981 Jul;56(7):496–508. doi: 10.1136/adc.56.7.496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Best L., Yates A. P., Tomlinson S. Stimulation of insulin secretion by glucose in the absence of diminished potassium (86Rb+) permeability. Biochem Pharmacol. 1992 Jun 9;43(11):2483–2485. doi: 10.1016/0006-2952(92)90330-l. [DOI] [PubMed] [Google Scholar]
  13. Bokvist K., Rorsman P., Smith P. A. Effects of external tetraethylammonium ions and quinine on delayed rectifying K+ channels in mouse pancreatic beta-cells. J Physiol. 1990 Apr;423:311–325. doi: 10.1113/jphysiol.1990.sp018024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Béguin P., Nagashima K., Nishimura M., Gonoi T., Seino S. PKA-mediated phosphorylation of the human K(ATP) channel: separate roles of Kir6.2 and SUR1 subunit phosphorylation. EMBO J. 1999 Sep 1;18(17):4722–4732. doi: 10.1093/emboj/18.17.4722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chutkow W. A., Simon M. C., Le Beau M. M., Burant C. F. Cloning, tissue expression, and chromosomal localization of SUR2, the putative drug-binding subunit of cardiac, skeletal muscle, and vascular KATP channels. Diabetes. 1996 Oct;45(10):1439–1445. doi: 10.2337/diab.45.10.1439. [DOI] [PubMed] [Google Scholar]
  16. Clement J. P., 4th, Kunjilwar K., Gonzalez G., Schwanstecher M., Panten U., Aguilar-Bryan L., Bryan J. Association and stoichiometry of K(ATP) channel subunits. Neuron. 1997 May;18(5):827–838. doi: 10.1016/s0896-6273(00)80321-9. [DOI] [PubMed] [Google Scholar]
  17. Dunne M. J. Effects of pinacidil, RP 49356 and nicorandil on ATP-sensitive potassium channels in insulin-secreting cells. Br J Pharmacol. 1990 Mar;99(3):487–492. doi: 10.1111/j.1476-5381.1990.tb12955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Dunne M. J., Kane C., Shepherd R. M., Sanchez J. A., James R. F., Johnson P. R., Aynsley-Green A., Lu S., Clement J. P., 4th, Lindley K. J. Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor. N Engl J Med. 1997 Mar 6;336(10):703–706. doi: 10.1056/NEJM199703063361005. [DOI] [PubMed] [Google Scholar]
  19. Dunne M. J., Petersen O. H. Potassium selective ion channels in insulin-secreting cells: physiology, pharmacology and their role in stimulus-secretion coupling. Biochim Biophys Acta. 1991 Mar 7;1071(1):67–82. doi: 10.1016/0304-4157(91)90012-l. [DOI] [PubMed] [Google Scholar]
  20. Dunne MJ, Cosgrove KE, Shepherd RM, Ämmälä C. Potassium Channels, Sulphonylurea Receptors and Control of Insulin Release. Trends Endocrinol Metab. 1999 May;10(4):146–152. doi: 10.1016/s1043-2760(98)00135-0. [DOI] [PubMed] [Google Scholar]
  21. Dörschner H., Brekardin E., Uhde I., Schwanstecher C., Schwanstecher M. Stoichiometry of sulfonylurea-induced ATP-sensitive potassium channel closure. Mol Pharmacol. 1999 Jun;55(6):1060–1066. doi: 10.1124/mol.55.6.1060. [DOI] [PubMed] [Google Scholar]
  22. Eichmann D., Hufnagel M., Quick P., Santer R. Treatment of hyperinsulinaemic hypoglycaemia with nifedipine. Eur J Pediatr. 1999 Mar;158(3):204–206. doi: 10.1007/s004310051049. [DOI] [PubMed] [Google Scholar]
  23. Froguel P, Velho G. Molecular Genetics of Maturity-onset Diabetes of the Young. Trends Endocrinol Metab. 1999 May;10(4):142–146. doi: 10.1016/s1043-2760(98)00134-9. [DOI] [PubMed] [Google Scholar]
  24. Gembal M., Gilon P., Henquin J. C. Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse B cells. J Clin Invest. 1992 Apr;89(4):1288–1295. doi: 10.1172/JCI115714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Glaser B., Kesavan P., Heyman M., Davis E., Cuesta A., Buchs A., Stanley C. A., Thornton P. S., Permutt M. A., Matschinsky F. M. Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med. 1998 Jan 22;338(4):226–230. doi: 10.1056/NEJM199801223380404. [DOI] [PubMed] [Google Scholar]
  26. Glaser B, Landau H, Permutt MA. Neonatal Hyperinsulinism. Trends Endocrinol Metab. 1999 Mar;10(2):55–61. doi: 10.1016/s1043-2760(98)00102-7. [DOI] [PubMed] [Google Scholar]
  27. Inagaki N., Gonoi T., Clement J. P., 4th, Namba N., Inazawa J., Gonzalez G., Aguilar-Bryan L., Seino S., Bryan J. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science. 1995 Nov 17;270(5239):1166–1170. doi: 10.1126/science.270.5239.1166. [DOI] [PubMed] [Google Scholar]
  28. Inagaki N., Gonoi T., Clement J. P., Wang C. Z., Aguilar-Bryan L., Bryan J., Seino S. A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron. 1996 May;16(5):1011–1017. doi: 10.1016/s0896-6273(00)80124-5. [DOI] [PubMed] [Google Scholar]
  29. Jonsson J., Carlsson L., Edlund T., Edlund H. Insulin-promoter-factor 1 is required for pancreas development in mice. Nature. 1994 Oct 13;371(6498):606–609. doi: 10.1038/371606a0. [DOI] [PubMed] [Google Scholar]
  30. Kalman K., Nguyen A., Tseng-Crank J., Dukes I. D., Chandy G., Hustad C. M., Copeland N. G., Jenkins N. A., Mohrenweiser H., Brandriff B. Genomic organization, chromosomal localization, tissue distribution, and biophysical characterization of a novel mammalian Shaker-related voltage-gated potassium channel, Kv1.7. J Biol Chem. 1998 Mar 6;273(10):5851–5857. doi: 10.1074/jbc.273.10.5851. [DOI] [PubMed] [Google Scholar]
  31. Kane C., Lindley K. J., Johnson P. R., James R. F., Milla P. J., Aynsley-Green A., Dunne M. J. Therapy for persistent hyperinsulinemic hypoglycemia of infancy. Understanding the responsiveness of beta cells to diazoxide and somatostatin. J Clin Invest. 1997 Oct 1;100(7):1888–1893. doi: 10.1172/JCI119718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kane C., Shepherd R. M., Squires P. E., Johnson P. R., James R. F., Milla P. J., Aynsley-Green A., Lindley K. J., Dunne M. J. Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy. Nat Med. 1996 Dec;2(12):1344–1347. doi: 10.1038/nm1296-1344. [DOI] [PubMed] [Google Scholar]
  33. Komatsu M., Aizawa T., Yokokawa N., Sato Y., Okada N., Takasu N., Yamada T. Mastoparan-induced hormone release from rat pancreatic islets. Endocrinology. 1992 Jan;130(1):221–228. doi: 10.1210/endo.130.1.1727698. [DOI] [PubMed] [Google Scholar]
  34. Kulkarni R. N., Brüning J. C., Winnay J. N., Postic C., Magnuson M. A., Kahn C. R. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell. 1999 Feb 5;96(3):329–339. doi: 10.1016/s0092-8674(00)80546-2. [DOI] [PubMed] [Google Scholar]
  35. Lang J. Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. Eur J Biochem. 1999 Jan;259(1-2):3–17. doi: 10.1046/j.1432-1327.1999.00043.x. [DOI] [PubMed] [Google Scholar]
  36. Lawson K. Potassium channel activation: a potential therapeutic approach? Pharmacol Ther. 1996;70(1):39–63. doi: 10.1016/0163-7258(96)00003-4. [DOI] [PubMed] [Google Scholar]
  37. Lebrun P., Antoine M. H., Ouedraogo R., Kane C., Dunne M., Hermann M., Herchuelz A., Masereel B., Delarge J., de Tullio P. Activation of ATP-dependent K+ channels and inhibition of insulin release: effect of BPDZ 62. J Pharmacol Exp Ther. 1996 Apr;277(1):156–162. [PubMed] [Google Scholar]
  38. Leech C. A., Habener J. F. A role for Ca2+-sensitive nonselective cation channels in regulating the membrane potential of pancreatic beta-cells. Diabetes. 1998 Jul;47(7):1066–1073. doi: 10.2337/diabetes.47.7.1066. [DOI] [PubMed] [Google Scholar]
  39. Leibiger B., Moede T., Schwarz T., Brown G. R., Köhler M., Leibiger I. B., Berggren P. O. Short-term regulation of insulin gene transcription by glucose. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9307–9312. doi: 10.1073/pnas.95.16.9307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lindley K. J., Dunne M. J., Kane C., Shepherd R. M., Squires P. E., James R. F., Johnson P. R., Eckhardt S., Wakeling E., Dattani M. Ionic control of beta cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade. Arch Dis Child. 1996 May;74(5):373–378. doi: 10.1136/adc.74.5.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. MacFarlane W. M., Chapman J. C., Shepherd R. M., Hashmi M. N., Kamimura N., Cosgrove K. E., O'Brien R. E., Barnes P. D., Hart A. W., Docherty H. M. Engineering a glucose-responsive human insulin-secreting cell line from islets of Langerhans isolated from a patient with persistent hyperinsulinemic hypoglycemia of infancy. J Biol Chem. 1999 Nov 26;274(48):34059–34066. doi: 10.1074/jbc.274.48.34059. [DOI] [PubMed] [Google Scholar]
  42. Macfarlane W. M., Cragg H., Docherty H. M., Read M. L., James R. F., Aynsley-Green A., Docherty K. Impaired expression of transcription factor IUF1 in a pancreatic beta-cell line derived from a patient with persistent hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis). FEBS Lett. 1997 Aug 18;413(2):304–308. doi: 10.1016/s0014-5793(97)00874-0. [DOI] [PubMed] [Google Scholar]
  43. Meissner T., Brune W., Mayatepek E. Persistent hyperinsulinaemic hypoglycaemia of infancy: therapy, clinical outcome and mutational analysis. Eur J Pediatr. 1997 Oct;156(10):754–757. doi: 10.1007/s004310050706. [DOI] [PubMed] [Google Scholar]
  44. Melloul D., Ben-Neriah Y., Cerasi E. Glucose modulates the binding of an islet-specific factor to a conserved sequence within the rat I and the human insulin promoters. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3865–3869. doi: 10.1073/pnas.90.9.3865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Miki T., Nagashima K., Seino S. The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells. J Mol Endocrinol. 1999 Apr;22(2):113–123. doi: 10.1677/jme.0.0220113. [DOI] [PubMed] [Google Scholar]
  46. Miki T., Nagashima K., Tashiro F., Kotake K., Yoshitomi H., Tamamoto A., Gonoi T., Iwanaga T., Miyazaki J., Seino S. Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10402–10406. doi: 10.1073/pnas.95.18.10402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Miki T., Tashiro F., Iwanaga T., Nagashima K., Yoshitomi H., Aihara H., Nitta Y., Gonoi T., Inagaki N., Miyazaki J. i. Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):11969–11973. doi: 10.1073/pnas.94.22.11969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Nestorowicz A., Glaser B., Wilson B. A., Shyng S. L., Nichols C. G., Stanley C. A., Thornton P. S., Permutt M. A. Genetic heterogeneity in familial hyperinsulinism. Hum Mol Genet. 1998 Jul;7(7):1119–1128. doi: 10.1093/hmg/7.7.1119. [DOI] [PubMed] [Google Scholar]
  49. Nestorowicz A., Inagaki N., Gonoi T., Schoor K. P., Wilson B. A., Glaser B., Landau H., Stanley C. A., Thornton P. S., Seino S. A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism. Diabetes. 1997 Nov;46(11):1743–1748. doi: 10.2337/diab.46.11.1743. [DOI] [PubMed] [Google Scholar]
  50. Nestorowicz A., Wilson B. A., Schoor K. P., Inoue H., Glaser B., Landau H., Stanley C. A., Thornton P. S., Clement J. P., 4th, Bryan J. Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews. Hum Mol Genet. 1996 Nov;5(11):1813–1822. doi: 10.1093/hmg/5.11.1813. [DOI] [PubMed] [Google Scholar]
  51. Otonkoski T., Ammälä C., Huopio H., Cote G. J., Chapman J., Cosgrove K., Ashfield R., Huang E., Komulainen J., Ashcroft F. M. A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland. Diabetes. 1999 Feb;48(2):408–415. doi: 10.2337/diabetes.48.2.408. [DOI] [PubMed] [Google Scholar]
  52. Patel Y. C., Srikant C. B. Somatostatin receptors. Trends Endocrinol Metab. 1997 Dec;8(10):398–405. doi: 10.1016/s1043-2760(97)00168-9. [DOI] [PubMed] [Google Scholar]
  53. Proks P., Ashcroft F. M. Phentolamine block of KATP channels is mediated by Kir6.2. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11716–11720. doi: 10.1073/pnas.94.21.11716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Roe M. W., Worley J. F., 3rd, Mittal A. A., Kuznetsov A., DasGupta S., Mertz R. J., Witherspoon S. M., 3rd, Blair N., Lancaster M. E., McIntyre M. S. Expression and function of pancreatic beta-cell delayed rectifier K+ channels. Role in stimulus-secretion coupling. J Biol Chem. 1996 Dec 13;271(50):32241–32246. doi: 10.1074/jbc.271.50.32241. [DOI] [PubMed] [Google Scholar]
  55. Roe M. W., Worley J. F., 3rd, Qian F., Tamarina N., Mittal A. A., Dralyuk F., Blair N. T., Mertz R. J., Philipson L. H., Dukes I. D. Characterization of a Ca2+ release-activated nonselective cation current regulating membrane potential and [Ca2+]i oscillations in transgenically derived beta-cells. J Biol Chem. 1998 Apr 24;273(17):10402–10410. doi: 10.1074/jbc.273.17.10402. [DOI] [PubMed] [Google Scholar]
  56. Rorsman P., Trube G. Calcium and delayed potassium currents in mouse pancreatic beta-cells under voltage-clamp conditions. J Physiol. 1986 May;374:531–550. doi: 10.1113/jphysiol.1986.sp016096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Ryan F., Devaney D., Joyce C., Nestorowicz A., Permutt M. A., Glaser B., Barton D. E., Thornton P. S. Hyperinsulinism: molecular aetiology of focal disease. Arch Dis Child. 1998 Nov;79(5):445–447. doi: 10.1136/adc.79.5.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Sakura H., Ammälä C., Smith P. A., Gribble F. M., Ashcroft F. M. Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart and skeletal muscle. FEBS Lett. 1995 Dec 27;377(3):338–344. doi: 10.1016/0014-5793(95)01369-5. [DOI] [PubMed] [Google Scholar]
  59. Service F. J., Natt N., Thompson G. B., Grant C. S., van Heerden J. A., Andrews J. C., Lorenz E., Terzic A., Lloyd R. V. Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes. J Clin Endocrinol Metab. 1999 May;84(5):1582–1589. doi: 10.1210/jcem.84.5.5645. [DOI] [PubMed] [Google Scholar]
  60. Sharma N., Crane A., Clement J. P., 4th, Gonzalez G., Babenko A. P., Bryan J., Aguilar-Bryan L. The C terminus of SUR1 is required for trafficking of KATP channels. J Biol Chem. 1999 Jul 16;274(29):20628–20632. doi: 10.1074/jbc.274.29.20628. [DOI] [PubMed] [Google Scholar]
  61. Shyng S. L., Ferrigni T., Shepard J. B., Nestorowicz A., Glaser B., Permutt M. A., Nichols C. G. Functional analyses of novel mutations in the sulfonylurea receptor 1 associated with persistent hyperinsulinemic hypoglycemia of infancy. Diabetes. 1998 Jul;47(7):1145–1151. doi: 10.2337/diabetes.47.7.1145. [DOI] [PubMed] [Google Scholar]
  62. Shyng S., Nichols C. G. Octameric stoichiometry of the KATP channel complex. J Gen Physiol. 1997 Dec;110(6):655–664. doi: 10.1085/jgp.110.6.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Smith P. A., Bokvist K., Arkhammar P., Berggren P. O., Rorsman P. Delayed rectifying and calcium-activated K+ channels and their significance for action potential repolarization in mouse pancreatic beta-cells. J Gen Physiol. 1990 Jun;95(6):1041–1059. doi: 10.1085/jgp.95.6.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Stanley C. A., Lieu Y. K., Hsu B. Y., Burlina A. B., Greenberg C. R., Hopwood N. J., Perlman K., Rich B. H., Zammarchi E., Poncz M. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med. 1998 May 7;338(19):1352–1357. doi: 10.1056/NEJM199805073381904. [DOI] [PubMed] [Google Scholar]
  65. Straub S. G., James R. F., Dunne M. J., Sharp G. W. Glucose activates both K(ATP) channel-dependent and K(ATP) channel-independent signaling pathways in human islets. Diabetes. 1998 May;47(5):758–763. doi: 10.2337/diabetes.47.5.758. [DOI] [PubMed] [Google Scholar]
  66. Straub S. G., James R. F., Dunne M. J., Sharp G. W. Glucose augmentation of mastoparan-stimulated insulin secretion in rat and human pancreatic islets. Diabetes. 1998 Jul;47(7):1053–1057. doi: 10.2337/diabetes.47.7.1053. [DOI] [PubMed] [Google Scholar]
  67. Thomas P. M., Cote G. J., Wohllk N., Haddad B., Mathew P. M., Rabl W., Aguilar-Bryan L., Gagel R. F., Bryan J. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science. 1995 Apr 21;268(5209):426–429. doi: 10.1126/science.7716548. [DOI] [PubMed] [Google Scholar]
  68. Thomas P. M., Wohllk N., Huang E., Kuhnle U., Rabl W., Gagel R. F., Cote G. J. Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy. Am J Hum Genet. 1996 Sep;59(3):510–518. [PMC free article] [PubMed] [Google Scholar]
  69. Tusnády G. E., Bakos E., Váradi A., Sarkadi B. Membrane topology distinguishes a subfamily of the ATP-binding cassette (ABC) transporters. FEBS Lett. 1997 Jan 27;402(1):1–3. doi: 10.1016/s0014-5793(96)01478-0. [DOI] [PubMed] [Google Scholar]
  70. Uhde I., Toman A., Gross I., Schwanstecher C., Schwanstecher M. Identification of the potassium channel opener site on sulfonylurea receptors. J Biol Chem. 1999 Oct 1;274(40):28079–28082. doi: 10.1074/jbc.274.40.28079. [DOI] [PubMed] [Google Scholar]
  71. Verkarre V., Fournet J. C., de Lonlay P., Gross-Morand M. S., Devillers M., Rahier J., Brunelle F., Robert J. J., Nihoul-Fékété C., Saudubray J. M. 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 Oct 1;102(7):1286–1291. doi: 10.1172/JCI4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Wollheim C. B., Sharp G. W. Regulation of insulin release by calcium. Physiol Rev. 1981 Oct;61(4):914–973. doi: 10.1152/physrev.1981.61.4.914. [DOI] [PubMed] [Google Scholar]
  73. Yajima H., Komatsu M., Schermerhorn T., Aizawa T., Kaneko T., Nagai M., Sharp G. W., Hashizume K. cAMP enhances insulin secretion by an action on the ATP-sensitive K+ channel-independent pathway of glucose signaling in rat pancreatic islets. Diabetes. 1999 May;48(5):1006–1012. doi: 10.2337/diabetes.48.5.1006. [DOI] [PubMed] [Google Scholar]
  74. 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 Jun;104(6):476–479. doi: 10.1007/s004390050990. [DOI] [PubMed] [Google Scholar]
  75. Zerangue N., Schwappach B., Jan Y. N., Jan L. Y. A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron. 1999 Mar;22(3):537–548. doi: 10.1016/s0896-6273(00)80708-4. [DOI] [PubMed] [Google Scholar]
  76. de Lonlay-Debeney P., Poggi-Travert F., Fournet J. C., Sempoux C., Dionisi Vici C., Brunelle F., Touati G., Rahier J., Junien C., Nihoul-Fékété C. Clinical features of 52 neonates with hyperinsulinism. N Engl J Med. 1999 Apr 15;340(15):1169–1175. doi: 10.1056/NEJM199904153401505. [DOI] [PubMed] [Google Scholar]

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