Kir6.2 variant E23K increases ATP-sensitive K+ channel activity and is associated with impaired insulin release and enhanced insulin sensitivity in adults with normal glucose tolerance

Diabetes

Volumn 58, Issue 8, 2009, Pages 1869-1878

  Villareal, Dennis T ^a   Koster, Joseph C ^a   Robertson, Heather ^a   Akrouh, Alejandro ^a   Miyake, Kazuaki ^b   Bell, Graeme I ^b   Patterson, Bruce W ^a   Nichols, Colin G ^a   Polonsky, Kenneth S ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; AMINO ACID; GLUTAMIC ACID; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR6.2; LYSINE;

ADULT; ARTICLE; CONTROLLED STUDY; ENZYME INHIBITION; FEMALE; GENOTYPE; GLUCOSE CLAMP TECHNIQUE; GLUCOSE TOLERANCE; HUMAN; HUMAN EXPERIMENT; INSULIN CLEARANCE; INSULIN RELEASE; INSULIN SENSITIVITY; ISOTOPE LABELING; MALE; MOLECULAR BIOLOGY; NON INSULIN DEPENDENT DIABETES MELLITUS; NORMAL HUMAN; ORAL GLUCOSE TOLERANCE TEST; PRIORITY JOURNAL; PROTEIN POLYMORPHISM;

ADULT; AMINO ACID SUBSTITUTION; ATP-BINDING CASSETTE TRANSPORTERS; CROSS-SECTIONAL STUDIES; FEMALE; GENETIC VARIATION; GENOTYPE; GLUCOSE CLAMP TECHNIQUE; GLUCOSE TOLERANCE TEST; HUMANS; INSULIN; KATP CHANNELS; MALE; MIDDLE AGED; POTASSIUM CHANNELS, INWARDLY RECTIFYING; RECEPTORS, DRUG; REFERENCE VALUES;

EID: 68049137605     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db09-0025     Document Type: Article

References (49)

1. Flanagan SE, Clauin S, Bellanne-Chantelot C, de LP, 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 2008
2. Perry JR, Frayling TM: New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function. Curr Opin Clin Nutr Metab Care 2008;11:371-377
3. Riedel MJ, Steckley DC, Light PE: Current status of the E23K Kir6.2 polymorphism: implications for type-2 diabetes. Hum Genet 2005;116:133-145
4. Sakura H, Wat N, Horton V, Millns H, Turner RC, Ashcroft FM: Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in while Caucasian subjects or evidence of abnormal function when expressed in vitro. Diabetologia 1996;39:1233-1236
5. Schwanstecher C, Meyer U, Schwanstecher M: K(IR)6.2 polymorphism predisposes to type 2 diabetes by inducing overactivity of pancreatic beta-cell ATP-sensitive K(+) channels. Diabetes 2002;51:875-879
6. Riedel MJ, Boora P, Steckley D, de VG, Light PE: 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 2003;52:2630-2635
7. Nielsen EM, Hansen L, Carstensen B, Echwald SM, Drivsholm T, Glumer C, Thorsteinsson B, Borch-Johnsen K, Hansen T, Pedersen O: The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes 2003;52:573-577
8. Florez JC, Burtt N, de Bakker PI, Almgren P, Tuomi T, Holmkvist J, Gaudet D, Hudson TJ, Schaffner SF, Daly MJ, Hirschhorn JN, Groop L, Altshuler D: Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes 2004;53:1360-1368
9. Chistiakov DA, Potapov VA, Khodirev DC, Shamkhalova MS, Shestakova MV, Nosikov VV: Genetic variations in the pancreatic ATP-sensitive potassium channel, beta-cell dysfunction, and susceptibility to type 2 diabetes. Acta Diabetol 2008
10. 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;95:10402-10406
11. Hansen L, Echwald SM, Hansen T, Urhammer SA, Clausen JO, Pedersen O: Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM. Diabetes 1997;46:508-512
12. Doi Y, Kubo M, Ninomiya T, Yonemoto K, Iwase M, Arima H, Hata J, Tanizaki Y, Iida M, Kiyohara Y: Impact of Kir6.2 E23K polymorphism on the development of type 2 diabetes in a general Japanese population: the Hisayama Study. Diabetes 2007;56:2829-2833
13. Florez JC, Jablonski KA, Kahn SE, Franks PW, Dabelea D, Hamman RF, Knowler WC, Nathan DM, Altshuler D. Type 2 diabetes-associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the Diabetes Prevention Program. Diabetes 2007;56:531-536
14. Palmer ND, Langefeld CD, Bryer-Ash M, Rotter JI, Taylor KD, Bowden DW. Association of the Kir6.2 E23K variant with reduced acute insulin response in African-Americans. J Clin Endocrinol Metab 2008;93:4979-4983
15. Byrne MM, Sturis J, Polonsky KS. Insulin secretion and clearance during low-dose graded glucose infusion. Am J Physiol 1995;268:E21-E27
16. Byrne MM, Sturis J, Clement K, Vionnet N, Pueyo ME, Stoffel M, Takeda J, Passa P, Cohen D, Bell GI. Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. J Clin Invest 1994;93:1120-1130
17. Klein S, Fontana L, Young VL, Coggan AR, Kilo C, Patterson BW, Mohammed BS. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 2004;350:2549-2557
18. Reeds DN, Yarasheski KE, Fontana L, Cade WT, Laciny E, DeMoss A, Patterson BW, Powderly WG, Klein S. Alterations in liver muscle and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia. Am J Physiol Endocrinol Metab 2006;290:E47-E53
19. Allison DB, Paultre F, Maggio C, Mezzitis N, Pi-Sunyer FX. The use of areas under curves in diabetes research. Diabetes Care 1995;18:245-250
20. Van Cauter E, Mestrez F, Sturis J, Polonsky KS. Estimation of insulin secretion rates from C-peptide levels: comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 1992;41:368-377
21. Breda E, Cavaghan MK, Toffolo G, Polonsky KS, Cobelli C. Oral glucose tolerance test minimal model indexes of β-cell function and insulin sensitivity. Diabetes 2001;50:150-158
22. Deivanayagam S, Mohammed BS, Vitola BE, Naguib GH, Keshen TH, Kirk EP, Klein S. Nonalcoholic fatty liver disease is associated with hepatic and skeletal muscle insulin resistance in overweight adolescents. Am J Clin Nutr 2008;88:257-262
23. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462-1470
24. Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006;355:2297-2307
25. Dalla MC, Caumo A, Basu R, Rizza R, Toffolo G, Cobelli C. Minimal model estimation of glucose absorption and insulin sensitivity from oral test: validation with a tracer method. Am J Physiol Endocrinol Metab 2004;287:E637-E643
26. Dalla MC, Caumo A, Cobelli C. The oral glucose minimal model: estimation of insulin sensitivity from a meal test. IEEE Trans Biomed Eng 2002;49:419-429
27. Tillil H, Shapiro ET, Miller MA, Karrison T, Frank BH, Galloway JA, Rubenstein AH, Polonsky KS. Dose-dependent effects of oral and intravenous glucose on insulin secretion and clearance in normal humans. Am J Physiol 1988;254:E349-E357
28. + channels in neonatal diabetes: implications for pharmacogenomic therapy. Diabetes 2005;54:2645-2654
29. Enkvetchakul D, Loussouarn G, Makhina E, Shyng SL, Nichols CG. The kinetic and physical basis of K(ATP) channel gating: toward a unified molecular understanding. Biophys J 2000;78:2334-2348
30. Neher E, Stevens CF. Conductance fluctuations and ionic pores in membranes. Annu Rev Biophys Bioeng 1977;6:345-381
31. Sigworth FJ. The variance of sodium current fluctuations at the node of Ranvier. J Physiol 1980;307:97-129
32. Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, Howard N, Srinivasan S, Silva JM, Molnes J, Edghill EL, Frayling TM, Temple IK, Mackay D, Shield JP, Sumnik Z, van RA, Wales JK, Clark P, Gorman S, Aisenberg J, Ellard S, Njolstad PR, Ashcroft FM, Hattersley AT. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 2004;350:1838-1849
33. Gloyn AL, Reimann F, Girard C, Edghill EL, Proks P, Pearson ER, Temple IK, Mackay DJ, Shield JP, Freedenberg D, Noyes K, Ellard S, Ashcroft FM, Gribble FM, Hattersley AT. Relapsing diabetes can result from moderately activating mutations in KCNJ11. Hum Mol Genet 2005;14:925-934
34. Proks P, Antcliff JF, Lippiat J, Gloyn AL, Hattersley AT, Ashcroft FM. Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features. Proc Natl Acad Sci U S A 2004;101:17539-17544
35. Gloyn AL, Weedon MN, Owen KR, Turner MJ, Knight BA, Hitman G, Walker M, Levy JC, Sampson M, Halford S, McCarthy MI, Hattersley AT, Frayling TM. Large-scale association studies of variants in genes encoding the pancreatic β-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes 2003;52:568-572
36. Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR, Walker M, Hitman GA, Morris AD, Doney AS; Wellcome Trust Case Control Consortium (WTCCC), McCarthy MI, Hattersley AT. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 2007;316:1336-1341
37. Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, Walters GB, Styrkarsdottir U, Gretarsdottir S, Emilsson V, Ghosh S, Baker A, Snorradottir S, Bjarnason H, Ng MC, Hansen T, Bagger Y, Wilensky RL, Reilly MP, Adeyemo A, Chen Y, Zhou J, Gudnason V, Chen G, Huang H, Lashley K, Doumatey A, So WY, Ma RC, Andersen G, Borch-Johnsen K, Jorgensen T, van Vliet-Ostaptchouk JV, Hofker MH, Wijmenga C, Christiansen C, Rader DJ, Rotimi C, Gurney M, Chan JC, Pedersen O, Sigurdsson G, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 2007;39:770-775
38. Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research, Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Boström K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Råstam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjögren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 2007;316:1331-1336
39. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV, Prentki M, Posner BI, Balding DJ, Meyre D, Polychronakos C, Froguel P. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 2007;445:881-885
40. Pocai A, Lam TK, Gutierrez-Juarez R, Obici S, Schwartz GJ, Bryan J, Aguilar-Bryan L, Rossetti L. Hypothalamic K(ATP) channels control hepatic glucose production. Nature 2005;434:1026-1031
41. Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, Xu C, Vianna CR, Balthasar N, Lee CE, Elmquist JK, Cowley MA, Lowell BB. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 2007;449:228-232
42. Fernandez-Castaner M, Molina A, Lopez-Jimenez L, Gomez JM, Soler J. Clinical presentation and early course of type 1 diabetes in patients with and without thyroid autoimmunity. Diabetes Care 1999;22:377-381
43. Stride A, Ellard S, Clark P, Shakespeare L, Salzmann M, Shepherd M, Hattersley AT. β-Cell dysfunction insulin sensitivity and glycosuria precede diabetes in hepatocyte nuclear factor-1α mutation carriers. Diabetes Care 2005;28:1751-1756
44. Duckworth WC, Hamel FG. Peavy DE. Hepatic metabolism of insulin. Am J Med 1998;85:71-76
45. Terris S, Steiner DF. Binding and degradation of 125I-insulin by rat hepatocytes. J Biol Chem 1975;250:8389-8398
46. Schwanstecher C, Schwanstecher M. Nucleotide sensitivity of pancreatic ATP-sensitive potassium channels and type 2 diabetes. Diabetes 2002;51(Suppl. 3):S358-S362
47. Sesti G, Laratta E, Cardellini M, Andreozzi F, Del GS, Irace C, Gnasso A, Grupillo M, Lauro R, Hribal ML, Perticone F, Marchetti P. The E23K variant of KCNJ11 encoding the pancreatic beta-cell adenosine 5′-triphosphate- sensitive potassium channel subunit Kir6.2 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes. J Clin Endocrinol Metab 2006;91:2334-2339
48. Holstein A, Hahn M, Stumvoll M, Kovacs P. The E23K variant of KCNJ11 and the risk for severe sulfonylurea-induced hypoglycemia in patients with type 2 diabetes. Horm Metab Res 2009;41(5):387-390
49. Melander A, Sartor G, Wahlin E, Schersten B, Bitzen PO. Serum tolbutamide and chlorpropamide concentrations in patients with diabetes mellitus. Br Med J 1978;1:142-144