Carriers of the TCF7L2 rs7903146 TT genotype have elevated levels of plasma glucose, serum proinsulin and plasma gastric inhibitory polypeptide (GIP) during a meal test

Diabetologia

Volumn 54, Issue 1, 2011, Pages 103-110

  Gjesing, A P ^a   Kjems, L L ^b   Vestmar, M A ^a   Grarup, N ^a   Linneberg, A ^c   Deacon, C F ^d   Holst, J J ^d   Pedersen, O ^a,d,e   Hansen, T ^a,f  

^a STENO DIABETES CENTER   (Denmark)

^b NOVARTIS PHARMA AG   (Switzerland)

^c GLOSTRUP UNIVERSITY HOSPITAL   (Denmark)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

^e AARHUS UNIVERSITY   (Denmark)

^f UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

Author keywords

Gene; Incretin; TCF7L2; Type 2 diabetes

Indexed keywords

GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 2; GLUCOSE; INSULIN; TRANSCRIPTION FACTOR 7 LIKE 2;

ADULT; ARTICLE; BODY MASS; CONTROLLED STUDY; GENE FREQUENCY; GENETIC ASSOCIATION; GENOTYPE; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE; HOMOZYGOSITY; HUMAN; INSULIN BLOOD LEVEL; INSULIN RELEASE; MAJOR CLINICAL STUDY; MALE; MEAL; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; TEST MEAL;

ALLELES; BLOOD GLUCOSE; GASTRIC INHIBITORY POLYPEPTIDE; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; MALE; MIDDLE AGED; PROINSULIN; TRANSCRIPTION FACTOR 7-LIKE 2 PROTEIN;

EID: 79953776123     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-010-1940-4     Document Type: Article

References (49)

1. Hattersley AT, Pearson ER (2006) Pharmacogenetics and beyond. The interaction of therapeutic response, β cell physiology and genetics in diabetes. Endocrinology 147:2657-2663
2. Florez JC (2008) Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: where are the insulin resistance genes? Diabetologia 51:1100-1110
3. Boesgaard TW, Gjesing AP, Grarup N et al (2009) Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients - EUGENE2 Study. PLoS ONE 4:e7236
4. Grarup N, Rose CS, Andersson EA et al (2007) Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies. Diabetes 56:3105-3111 (Pubitemid 350223649)
5. Grarup N, Andersen G, Krarup NT et al (2008) Association testing of novel type 2 diabetes risk-alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes. Diabetes 57:2534-2540
6. Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889-894 (Pubitemid 46764279)
7. Rung J, Cauchi S, Albrechtsen A et al (2009) Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet 41:1110-1115
8. Helgason A, Pálsson S, Thorleifsson G et al (2007) Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat Genet 39:218-225 (Pubitemid 46184353)
9. Grant SF, Thorleifsson G, Reynisdottir I et al (2009) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38:320-323
10. Osmark P, Hansson O, Jonsson A, Rönn T, Groop L, Renström E (2009) Unique splicing pattern of the TCF7L2 gene in human pancreatic islets. Diabetologia 52:850-854
11. Prokunina-Olsson L, Welch C, Hansson O et al (2009) Tissue-specific alternative splicing of TCF7L2. Hum Mol Genet 18: 3795-3804
12. Clevers H (2006) Wnt/β-Catenin signaling in development and disease. Cell 127:469-480
13. Yi F, Brubaker PL, Jin T (2005) TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase-3beta. J Biol Chem 280:1457-1464
14. García-Martínez JM, Chocarro-Calvo A, Moya CM, García-Jiménez C (2009) WNT/beta-catenin increases the production of incretins by entero-endocrine cells. Diabetologia 52:1913-1924
15. Kirkpatrick CL, Marchetti P, Purrello F et al (2010) Type 2 diabetes susceptibility gene expression in normal or diabetic sorted human alpha and beta cells: correlations with age or BMI of islet donors. PLoS ONE 5:e11053
16. Nauck MA, Homberger E, Siegel EG et al (1986) Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 63:492-498 (Pubitemid 16035703)
17. Dunning BE, Gerich JE (2007) The role of alpha-cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications. Endocr Rev 28:253-283 (Pubitemid 46984828)
18. Pearson ER (2009) Translating TCF7L2: from gene to function. Diabetologia 52:1227-1230
19. Schäfer SA, Tschritter O, Machicao F et al (2007) Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia 50:2443-2450 (Pubitemid 350060632)
20. Villareal DT, Robertson H, Bell GI et al (2010) TCF7L2 variant rs7903146 affects the risk of type 2 diabetes by modulating incretin action. Diabetes 59:479-485
21. Pilgaard K, Jensen CB, Schou JH et al (2009) The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. Diabetologia 52:1298-1307
22. Loos RJ, Franks PW, Francis RW et al (2007) TCF7L2 polymorphisms modulate proinsulin levels and beta-cell function in a British Europid population. Diabetes 56:1943-1947 (Pubitemid 47025464)
23. González-Sánchez JL, Martínez-Larrad MT, Zabena C, Pérez-Barba M, Serrano-Ríos M (2008) Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin:insulin ratio in the Spanish population. Diabetologia 51:1993-1997
24. Kirchhoff K, Machicao F, Haupt A et al (2008) Polymorphisms in the TCF7L2, CDKAL1 and SLC30A8 genes are associated with impaired proinsulin conversion. Diabetologia 51:597-601
25. Stancáková A, Kuulasmaa T, Paananen J et al (2009) Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes 58:2129-2136
26. Stolerman ES, Manning AK, McAteer JB et al (2009) TCF7L2 variants are associated with increased proinsulin/insulin ratios but not obesity traits in the Framingham Heart Study. Diabetologia 52:614-620
27. Shu L, Matveyenko AV, Kerr-Conte J, Cho JH, McIntosh CH, Maedler K (2009) Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet 18:2388-2399
28. Lyssenko V, Lupi R, Marchetti P et al (2007) Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest 117:2155-2163 (Pubitemid 47219560)
29. Lee SH, Demeterco C, Geron I, Abrahamsson A, Levine F, Itkin-Ansari P (2008) Islet specific Wnt activation in human type II diabetes. Exp Diabetes Res 2008:728763
30. Jørgensen T, Borch-Johnsen K, Thomsen TF, Ibsen H, Glümer C, Pisinger C (2003) A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur J Cardiovasc Prev Rehabil 10:377-386 (Pubitemid 38037253)
31. Orskov C, Rabenhøj L, Wettergren A, Kofod H, Holst JJ (1994) Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes 43:535-539 (Pubitemid 24096293)
32. Deacon CF, Nauck MA, Meier J, Hücking K, Holst JJ (2000) Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide. J Clin Endocrinol Metab 85:3575-3581
33. Hartmann B, Johnsen AH, Orskov C, Adelhorst K, Thim L, Holst JJ (2000) Structure, measurement, and secretion of human glucagon-like peptide-2. Peptides 21:73-80 (Pubitemid 30126045)
34. Holst JJ (1982) Evidence that enteroglucagon (II) is identical with the C-terminal sequence (residues 33-69) of glicentin. Biochem J 207:381-388
35. Hovorka R, Koukkou E, Southerden D, Powrie JK, Young MA (1998) Measuring pre-hepatic insulin secretion using a population model of C-peptide kinetics: accuracy and required sampling schedule. Diabetologia 41:548-554 (Pubitemid 28206825)
36. van Cauter E, Mestrez F, Sturis J, Polonsky KS (1992) Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 41:368-377
37. Hovorka R, Soons PA, Young MA (1996) ISEC: a program to calculate insulin secretion. Comput Methods Programs Biomed 50:253-264 (Pubitemid 26308809)
38. Munoz J, Lok KH, Gower BA et al (2006) Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with reduced insulin secretion in nondiabetic women. Diabetes 55:3630-3634 (Pubitemid 44923627)
39. Palmer ND, Lehtinen AB, Langefeld CD et al (2008) Association of TCF7L2 gene polymorphisms with reduced acute insulin response in Hispanic Americans. J Clin Endocrinol Metab 93:304-309
40. Rasmussen-Torvik LJ, Pankow JS, Jacobs DR Jr, Sinaiko AR (2009) Preliminary report: No association between TCF7L2 rs7903146 and euglycemic-clamp-derived insulin sensitivity in a mixed-age cohort. Metabolism 58:1369-1371
41. Saxena R, Gianniny L, Burtt NP et al (2006) Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals. Diabetes 55:2890-2895 (Pubitemid 44923692)
42. Wang J, Kuusisto J, Vänttinen M et al (2007) Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion. Diabetologia 50:1192-2000
43. Wegner L, Hussain MS, Pilgaard K et al (2008) Impact of TCF7L2 rs7903146 on insulin secretion and action in young and elderly Danish twins. J Clin Endocrinol Metab 93:4013-4019
44. Florez JC, Jablonski KA, Bayley N et al (2006) Diabetes Prevention Program Research Group. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 355:241-250 (Pubitemid 44079339)
45. Meier JJ, NAUCk MA, Pott A et al (2006) Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. Gastroenterology 130:44-54 (Pubitemid 43049834)
46. Sinclair EM, Drucker DJ (2005) Proglucagon-derived peptides: mechanisms of action and therapeutic potential. Physiology (Bethesda) 20:357-365 (Pubitemid 41457401)
47. Knop FK (2009) Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signalling? Diabetologia 52:2270-2276
48. NAUCk MA (2009) Unraveling the science of incretin biology. Eur J Intern Med 20(Suppl 2):S303-S308
49. Irwin N, Flatt PR (2009) Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications. Diabetologia 52:1724-1731