Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-26T22:39:34.012Z Has data issue: false hasContentIssue false
  • English
  • Français

Molecular cell biology of KATP channels: implications for neonatal diabetes

Published online by Cambridge University Press:  01 August 2007

Andrew J. Smith ,
Tarvinder K. Taneja ,
Jamel Mankouri  and
Asipu Sivaprasadarao
Andrew J. Smith
Affiliation:
Institute of Membrane and Systems Biology, University of Leeds, Leeds, UK.
Tarvinder K. Taneja
Affiliation:
Institute of Membrane and Systems Biology, University of Leeds, Leeds, UK.
Jamel Mankouri
Affiliation:
Institute of Membrane and Systems Biology, University of Leeds, Leeds, UK.
Asipu Sivaprasadarao*
Affiliation:
Institute of Membrane and Systems Biology, University of Leeds, Leeds, UK.
*
*Corresponding author: Asipu Sivaprasadarao, Institute of Membrane and Systems Biology, University of Leeds, Leeds, LS2 9JT, UK. Tel: +44 (0)113 3434 326; Fax: +44 (0)113 3434 228; E-mail: a.sivaprasadarao@leeds.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

ATP-sensitive potassium (KATP) channels play a key role in the regulation of insulin secretion by coupling glucose metabolism to the electrical activity of pancreatic β-cells. To generate an electric signal of suitable magnitude, the plasma membrane of the β-cell must contain an appropriate number of channels. An inadequate number of channels can lead to congenital hyperinsulinism, whereas an excess of channels can result in the opposite condition, neonatal diabetes. KATP channels are made up of four subunits each of Kir6.2 and the sulphonylurea receptor (SUR1), encoded by the genes KCNJ11 and ABCC8, respectively. Following synthesis, the subunits must assemble into an octameric complex to be able to exit the endoplasmic reticulum and reach the plasma membrane. While this biosynthetic pathway ensures supply of channels to the cell surface, an opposite pathway, involving clathrin-mediated endocytosis, removes channels back into the cell. The balance between these two processes, perhaps in conjunction with endocytic recycling, would dictate the channel density at the cell membrane. In this review, we discuss the molecular signals that contribute to this balance, and how an imbalance could lead to a disease state such as neonatal diabetes.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 9 , Issue 21 , August 2007 , pp. 1 - 17
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1MacDonald, P.E., Joseph, J.W. and Rorsman, P. (2005) Glucose-sensing mechanisms in pancreatic beta-cells. Philos Trans R Soc Lond B Biol Sci 360, 2211–2225CrossRefGoogle ScholarPubMed
2Nichols, C.G. (2006) KATP channels as molecular sensors of cellular metabolism. Nature 440, 470–476CrossRefGoogle ScholarPubMed
3Ashcroft, F.M. (2005) ATP-sensitive potassium channelopathies: focus on insulin secretion. J Clin Invest 115, 2047–2058CrossRefGoogle ScholarPubMed
4Straub, S.G. and Sharp, G.W. (2002) Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab Res Rev 18, 451–463CrossRefGoogle ScholarPubMed
5Taguchi, N. et al. (1995) Mechanism of glucose-induced biphasic insulin release: physiological role of adenosine triphosphate-sensitive K+ channel-independent glucose action. Endocrinology 136, 3942–3948CrossRefGoogle ScholarPubMed
6Aizawa, T. et al. (1998) Glucose action ‘beyond ionic events’ in the pancreatic beta cell. Trends Pharmacol Sci 19, 496–499CrossRefGoogle ScholarPubMed
7Dunne, M.J. et al. (2004) Hyperinsulinism in infancy: from basic science to clinical disease. Physiol Rev 84, 239–275CrossRefGoogle ScholarPubMed
8Nichols, C.G. et al. (1996) Adenosine diphosphate as an intracellular regulator of insulin secretion. Science 272, 1785–1787CrossRefGoogle ScholarPubMed
9Shyng, S.L. et al. (1998) Functional analyses of novel mutations in the sulfonylurea receptor 1 associated with persistent hyperinsulinemic hypoglycemia of infancy. Diabetes 47, 1145–1151CrossRefGoogle ScholarPubMed
10Partridge, C.J., Beech, D.J. and Sivaprasadarao, A. (2001) Identification and pharmacological correction of a membrane trafficking defect associated with a mutation in the sulfonylurea receptor causing familial hyperinsulinism. J Biol Chem 276, 35947–35952CrossRefGoogle ScholarPubMed
11Cartier, E.A. et al. (2001) 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 U S A 98, 2882–2887CrossRefGoogle ScholarPubMed
12Taschenberger, G. et al. (2002) Identification of a familial hyperinsulinism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels. J Biol Chem 277, 17139–17146CrossRefGoogle ScholarPubMed
13Remedi, M.S. et al. (2006) Hyperinsulinism in mice with heterozygous loss of K(ATP) channels. Diabetologia 49, 2368–2378CrossRefGoogle ScholarPubMed
14Remedi, M.S. et al. (2004) Diet-induced glucose intolerance in mice with decreased beta-cell ATP-sensitive K+ channels. Diabetes 53, 3159–3167CrossRefGoogle ScholarPubMed
15Gloyn, A.L. et al. (2004) Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 350, 1838–1849CrossRefGoogle ScholarPubMed
16Gloyn, A.L. et al. (2005) Relapsing diabetes can result from moderately activating mutations in KCNJ11. Hum Mol Genet 14, 925–934CrossRefGoogle ScholarPubMed
17Huopio, H. et al. (2003) A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. Lancet 361, 301–307CrossRefGoogle ScholarPubMed
18Ashcroft, F.M. (2006) K(ATP) channels and insulin secretion: a key role in health and disease. Biochem Soc Trans 34, 243–246CrossRefGoogle ScholarPubMed
19Ashcroft, F. and Rorsman, P. (2004) Type 2 diabetes mellitus: not quite exciting enough? Hum Mol Genet 13 Spec No 1, R21–R31CrossRefGoogle ScholarPubMed
20Riedel, M.J. et al. (2003) Kir6.2 polymorphisms sensitize beta-cell ATP-sensitive potassium channels to activation by acyl CoAs: a possible cellular mechanism for increased susceptibility to type 2 diabetes? Diabetes 52, 2630–2635CrossRefGoogle ScholarPubMed
21Riedel, M.J., Steckley, D.C. and Light, P.E. (2005) Current status of the E23K Kir6.2 polymorphism: implications for type-2 diabetes. Hum Genet 116, 133–145CrossRefGoogle ScholarPubMed
22Aguilar-Bryan, L. and Bryan, J. (1999) Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev 20, 101–135Google ScholarPubMed
23Inagaki, N. et al. (1995) Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J Biol Chem 270, 5691–5694CrossRefGoogle ScholarPubMed
24Tucker, S.J. et al. (1997) Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor. Nature 387, 179–183CrossRefGoogle ScholarPubMed
25MacKinnon, R. (2004) Nobel Lecture. Potassium channels and the atomic basis of selective ion conduction. Biosci Rep 24, 75–100CrossRefGoogle ScholarPubMed
26Kuo, A. et al. (2003) Crystal structure of the potassium channel KirBac1. 1 in the closed state. Science 300, 1922–1926CrossRefGoogle ScholarPubMed
27Nishida, M. and MacKinnon, R. (2002) Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1. 8 A resolution. Cell 111, 957–965CrossRefGoogle Scholar
28Antcliff, J.F. et al. (2005) Functional analysis of a structural model of the ATP-binding site of the KATP channel Kir6.2 subunit. EMBO J 24, 229–239CrossRefGoogle ScholarPubMed
29Aguilar-Bryan, L. et al. (1995) Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science 268, 423–426CrossRefGoogle ScholarPubMed
30Tusnady, G.E. et al. (1997) Membrane topology distinguishes a subfamily of the ATP-binding cassette (ABC) transporters. FEBS Lett 402, 1–3CrossRefGoogle ScholarPubMed
31Conti, L.R. et al. (2001) Transmembrane topology of the sulfonylurea receptor SUR1. J Biol Chem 276, 41270–41278CrossRefGoogle ScholarPubMed
32Babenko, A.P. and Bryan, J. (2002) SUR-dependent modulation of KATP channels by an N-terminal KIR6.2 peptide. Defining intersubunit gating interactions. J Biol Chem 277, 43997–44004CrossRefGoogle ScholarPubMed
33Fang, K., Csanady, L. and Chan, K.W. (2006) The N-terminal transmembrane domain (TMD0) and a cytosolic linker (L0) of sulphonylurea receptor define the unique intrinsic gating of KATP channels. J Physiol 576, 379–389CrossRefGoogle Scholar
34Chan, K.W., Zhang, H. and Logothetis, D.E. (2003) N-terminal transmembrane domain of the SUR controls trafficking and gating of Kir6 channel subunits. EMBO J 22, 3833–3843CrossRefGoogle ScholarPubMed
35Mikhailov, M.V. et al. (2005) 3-D structural and functional characterization of the purified KATP channel complex Kir6.2-SUR1. EMBO J 24, 4166–4175CrossRefGoogle ScholarPubMed
36Ueda, K., Inagaki, N. and Seino, S. (1997) MgADP antagonism to Mg2+-independent ATP binding of the sulfonylurea receptor SUR1. J Biol Chem 272, 22983–22986CrossRefGoogle ScholarPubMed
37Gribble, F.M. et al. (1998) MgATP activates the beta cell KATP channel by interaction with its SUR1 subunit. Proc Natl Acad Sci U S A 95, 7185–7190CrossRefGoogle ScholarPubMed
38Matsuo, M., Kimura, Y. and Ueda, K. (2005) KATP channel interaction with adenine nucleotides. J Mol Cell Cardiol 38, 907–916CrossRefGoogle ScholarPubMed
39Babenko, A.P., Gonzalez, G. and Bryan, J. (2000) Pharmaco-topology of sulfonylurea receptors. Separate domains of the regulatory subunits of K(ATP) channel isoforms are required for selective interaction with K(+) channel openers. J Biol Chem 275, 717–720CrossRefGoogle Scholar
40Proks, P. et al. (2002) Sulfonylurea stimulation of insulin secretion. Diabetes 51 Suppl 3, S368–S376CrossRefGoogle ScholarPubMed
41Ashcroft, F.M. and Gribble, F.M. (2000) New windows on the mechanism of action of K(ATP) channel openers. Trends Pharmacol Sci 21, 439–445CrossRefGoogle ScholarPubMed
42Ueda, K. et al. (1999) Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide. Proc Natl Acad Sci U S A 96, 1268–1272CrossRefGoogle ScholarPubMed
43Lin, Y.W. et al. (2006) A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels. J Biol Chem 281, 3006–3012CrossRefGoogle ScholarPubMed
44Ribalet, B. et al. (2005) Regulation of the ATP-sensitive K channel Kir6.2 by ATP and PIP(2). J Mol Cell Cardiol 39, 71–77CrossRefGoogle ScholarPubMed
45Gribble, F.M. et al. (1998) Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA. J Biol Chem 273, 26383–26387CrossRefGoogle ScholarPubMed
46Branstrom, R. et al. (1998) Long chain coenzyme A esters activate the pore-forming subunit (Kir6.2) of the ATP-regulated potassium channel. J Biol Chem 273, 31395–31400CrossRefGoogle ScholarPubMed
47Mankouri, J. et al. (2006) Kir6.2 mutations causing neonatal diabetes prevent endocytosis of ATP-sensitive potassium channels. EMBO J 25, 4142–4151CrossRefGoogle ScholarPubMed
48Seino, S. and Miki, T. (2003) Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog Biophys Mol Biol 81, 133–176CrossRefGoogle ScholarPubMed
49Lantz, K.A. et al. (2004) Foxa2 regulates multiple pathways of insulin secretion. J Clin Invest 114, 512–520CrossRefGoogle ScholarPubMed
50Smith, A.J. et al. (2006) Increased ATP-sensitive K+ channel expression during acute glucose deprivation. Biochem Biophys Res Commun 348, 1123–1131CrossRefGoogle ScholarPubMed
51Moritz, W. et al. (2001) Regulated expression of adenosine triphosphate-sensitive potassium channel subunits in pancreatic beta-cells. Endocrinology 142, 129–138CrossRefGoogle ScholarPubMed
52Jonas, J.C. et al. (1999) Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes. J Biol Chem 274, 14112–14121CrossRefGoogle Scholar
53Zerangue, N. et al. (1999) A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron 22, 537–548CrossRefGoogle ScholarPubMed
54Michelsen, K., Yuan, H. and Schwappach, B. (2005) Hide and run. Arginine-based endoplasmic-reticulum-sorting motifs in the assembly of heteromultimeric membrane proteins. EMBO Rep 6, 717–722Google ScholarPubMed
55Yuan, H., Michelsen, K. and Schwappach, B. (2003) 14-3-3 dimers probe the assembly status of multimeric membrane proteins. Curr Biol 13, 638–646CrossRefGoogle ScholarPubMed
56Heusser, K. et al. (2006) Scavenging of 14-3-3 proteins reveals their involvement in the cell-surface transport of ATP-sensitive K+ channels. J Cell Sci 119, 4353–4363CrossRefGoogle ScholarPubMed
57Sharma, N. et al. (1999) The C terminus of SUR1 is required for trafficking of KATP channels. J Biol Chem 274, 20628–20632CrossRefGoogle Scholar
58Conti, L.R., Radeke, C.M. and Vandenberg, C.A. (2002) Membrane targeting of ATP-sensitive potassium channel. Effects of glycosylation on surface expression. J Biol Chem 277, 25416–25422CrossRefGoogle ScholarPubMed
59Yan, F.F. et al. (2005) Role of ubiquitin-proteasome degradation pathway in biogenesis efficiency of {beta}-cell ATP-sensitive potassium channels. Am J Physiol Cell Physiol 289, C1351–C1359CrossRefGoogle ScholarPubMed
60Marchese, A. et al. (2003) The ins and outs of G protein-coupled receptor trafficking. Trends Biochem Sci 28, 369–376CrossRefGoogle ScholarPubMed
61Nong, Y., Huang, Y.Q. and Salter, M.W. (2004) NMDA receptors are movin' in. Curr Opin Neurobiol 14, 353–361CrossRefGoogle Scholar
62Hu, K. et al. (2003) ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase C. Neuron 38, 417–432CrossRefGoogle ScholarPubMed
63Conner, S.D. and Schmid, S.L. (2003) Regulated portals of entry into the cell. Nature 422, 37–44CrossRefGoogle ScholarPubMed
64Kennedy, M.J. and Ehlers, M.D. (2006) Organelles and Trafficking Machinery for Postsynaptic Plasticity. Annu Rev Neurosci 29, 325–362CrossRefGoogle ScholarPubMed
65Bonifacino, J.S. and Traub, L.M. (2003) Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu Rev Biochem 72, 395–447CrossRefGoogle ScholarPubMed
66McMahon, H.T. and Mills, I.G. (2004) COP and clathrin-coated vesicle budding: different pathways, common approaches. Curr Opin Cell Biol 16, 379–391CrossRefGoogle ScholarPubMed
67Drake, M.T., Shenoy, S.K. and Lefkowitz, R.J. (2006) Trafficking of G protein-coupled receptors. Circ Res 99, 570–582CrossRefGoogle ScholarPubMed
68Nesher, R. et al. (2002) Beta-cell protein kinases and the dynamics of the insulin response to glucose. Diabetes 51 Suppl 1, S68–S73CrossRefGoogle ScholarPubMed
69Pfeffer, S. (2003) Membrane domains in the secretory and endocytic pathways. Cell 112, 507–517CrossRefGoogle ScholarPubMed
70Smith, A.J. et al. (2006) Recycling of Internalised ATP-Sensitive Potassium Channels. Biophys J 90, Pos-1106Google Scholar
71Rohn, W.M. et al. (2000) Bi-directional trafficking between the trans-Golgi network and the endosomal/lysosomal system. J Cell Sci 113, 2093–2101CrossRefGoogle ScholarPubMed
72Schapiro, F.B. et al. (2004) Role of cytoplasmic domain serines in intracellular trafficking of furin. Mol Biol Cell 15, 2884–2894CrossRefGoogle ScholarPubMed
73Ghosh, P. and Kornfeld, S. (2004) The GGA proteins: key players in protein sorting at the trans-Golgi network. Eur J Cell Biol 83, 257–262CrossRefGoogle ScholarPubMed
74Zerial, M. and McBride, H. (2001) Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2, 107–117CrossRefGoogle ScholarPubMed
75Dugani, C.B. and Klip, A. (2005) Glucose transporter 4: cycling, compartments and controversies. EMBO Rep 6, 1137–1142CrossRefGoogle ScholarPubMed
76Drake, M.T., Shenoy, S.K. and Lefkowitz, R.J. (2006) Trafficking of G protein-coupled receptors. Circ Res 99, 570–582CrossRefGoogle ScholarPubMed
77Gaborik, Z. and Hunyady, L. (2004) Intracellular trafficking of hormone receptors. Trends Endocrinol Metab 15, 286–293CrossRefGoogle ScholarPubMed
78Geng, X. et al. (2003) The insulin secretory granule is the major site of K(ATP) channels of the endocrine pancreas. Diabetes 52, 767–776CrossRefGoogle ScholarPubMed
79Varadi, A. et al. (2006) Intracellular ATP-sensitive K(+) channels in mouse pancreatic beta cells: against a role in organelle cation homeostasis. Diabetologia 49, 1567–1577CrossRefGoogle ScholarPubMed
80Jiang, M.T. et al. (2006) Characterization of human cardiac mitochondrial ATP-sensitive potassium channel and its regulation by phorbol ester in vitro. Am J Physiol Heart Circ Physiol 290, H1770–H1776CrossRefGoogle ScholarPubMed
81Minners, J., McLeod, C.J. and Sack, M.N. (2003) Mitochondrial plasticity in classical ischemic preconditioning-moving beyond the mitochondrial KATP channel. Cardiovasc Res 59, 1–6CrossRefGoogle ScholarPubMed
82Shield, J.P. (2000) Neonatal diabetes: new insights into aetiology and implications. Horm Res 53 Suppl 1, 7–11Google ScholarPubMed
83Ashcroft, F.M. (2006) K(ATP) channels and insulin secretion: a key role in health and disease. Biochem Soc Trans 34, 243–246CrossRefGoogle ScholarPubMed
84Proks, P. et al. (2004) Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features. Proc Natl Acad Sci U S A 101, 17539–17544CrossRefGoogle ScholarPubMed
85Proks, P. et al. (2005) A gating mutation at the internal mouth of the Kir6.2 pore is associated with DEND syndrome. EMBO Rep 6, 470–475CrossRefGoogle ScholarPubMed
86Babenko, A.P. et al. (2006) Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med 355, 456–466CrossRefGoogle ScholarPubMed
87Stanik, J. et al. (2007) Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers. J Clin Endocrinol Metab 92, 1276–1282CrossRefGoogle ScholarPubMed
88Zung, A. et al. (2004) Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2. J Clin Endocrinol Metab 89, 5504–5507CrossRefGoogle Scholar
89Tammaro, P. et al. (2005) Kir6.2 mutations causing neonatal diabetes provide new insights into Kir6.2-SUR1 interactions. EMBO J 24, 2318–2330CrossRefGoogle ScholarPubMed
90Glaser, B. et al. (2000) Genetics of neonatal hyperinsulinism. Arch Dis Child Fetal Neonatal Ed 82, F79–F86CrossRefGoogle ScholarPubMed
91Yan, F.F., Casey, J. and Shyng, S.L. (2006) Sulfonylureas correct trafficking defects of disease-causing ATP-sensitive potassium channels by binding to the channel complex. J Biol Chem 281, 33403–33413CrossRefGoogle Scholar
92Loo, T.W and Clarke, D.M. (2007) Chemical and pharmacological chaperones as new therapeutic agents. Expert Rev Mol Med 9, 1–18CrossRefGoogle ScholarPubMed
93Zerial, M. and McBride, H. (2001) Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2, 107–117CrossRefGoogle ScholarPubMed
94Sagen, J.V. et al. (2004) Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy. Diabetes 53, 2713–2718CrossRefGoogle ScholarPubMed
95Proks, P. et al. (2006) Functional Effects of Mutations at F35 in the NH2-terminus of Kir6.2 (KCNJ11), Causing Neonatal Diabetes, and Response to Sulfonylurea Therapy. Diabetes 55, 1731–1737CrossRefGoogle ScholarPubMed
96Vaxillaire, M. et al. (2004) Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients. Diabetes 53, 2719–2722CrossRefGoogle Scholar
97Proks, P., Girard, C. and Ashcroft, F.M. (2005) Functional effects of KCNJ11 mutations causing neonatal diabetes: enhanced activation by MgATP. Hum Mol Genet 14, 2717–2726CrossRefGoogle ScholarPubMed
98Girard, C.A. et al. (2006) Functional analysis of six Kir6.2 (KCNJ11) mutations causing neonatal diabetes. Pflugers Arch 453, 323–332CrossRefGoogle ScholarPubMed
99Massa, O. et al. (2005) KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes. Hum Mutat 25, 22–27CrossRefGoogle ScholarPubMed
100Shimomura, K. et al. (2006) Mutations at the Same Residue (R50) of Kir6.2 (KCNJ11) That Cause Neonatal Diabetes Produce Different Functional Effects. Diabetes 55, 1705–1712CrossRefGoogle ScholarPubMed
101Flanagan, S.E. et al. (2006) Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype. Diabetologia 49, 1190–1197CrossRefGoogle ScholarPubMed
102Gloyn, A.L. et al. (2006) KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features. Eur J Hum Genet 14, 824–830CrossRefGoogle ScholarPubMed
103Proks, P. et al. (2006) A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes. Hum Mol Genet 15, 1793–1800CrossRefGoogle ScholarPubMed
104Yorifuji, T. et al. (2005) The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus. J Clin Endocrinol Metab 90, 3174–3178CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

The Online Mendelian Inheritance in Man database lists human genetic mutations associated with KCNJ11 and ABCC8 and genetic disorders, with references and related links:

Aridor, M. and Hannan, L.A. (2002) Traffic jams II: an update of diseases of intracellular transport. Traffic 3, 781–790CrossRefGoogle Scholar
Sanders, C.R. and Myers, J.K. (2004) Disease-related misassembly of membrane proteins. Annu Rev Biophys Biomol Struct 33, 25–51CrossRefGoogle ScholarPubMed
Ellgaard, L. and Helenius, A. (2003) Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4, 181–191CrossRefGoogle ScholarPubMed
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600937 (KCNJ11)Google Scholar
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600509 (ABCC8)Google Scholar
Aridor, M. and Hannan, L.A. (2002) Traffic jams II: an update of diseases of intracellular transport. Traffic 3, 781–790CrossRefGoogle Scholar
Sanders, C.R. and Myers, J.K. (2004) Disease-related misassembly of membrane proteins. Annu Rev Biophys Biomol Struct 33, 25–51CrossRefGoogle ScholarPubMed
Ellgaard, L. and Helenius, A. (2003) Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4, 181–191CrossRefGoogle ScholarPubMed
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600937 (KCNJ11)Google Scholar
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600509 (ABCC8)Google Scholar