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Erschienen in: Diabetologia 12/2004

01.12.2004 | Article

Common polymorphisms of the PPAR-γ2 (Pro12Ala) and PGC-1α (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial

verfasst von: L. Andrulionytè, J. Zacharova, J.-L. Chiasson, M. Laakso, for the STOP-NIDDM Study Group

Erschienen in: Diabetologia | Ausgabe 12/2004

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Abstract

Aim/hypothesis

We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor γ2 (PPAR-γ2; Pro12Ala) and in PPAR-γ coactivator 1α (PGC-1α; Gly482Ser) genes on the conversion from impaired glucose tolerance to type 2 diabetes in participants in the STOP-NIDDM trial. This trial aimed to study the effect of acarbose in the prevention of type 2 diabetes.

Methods

Genotyping was performed in 770 study subjects whose DNA was available. The Gly482Ser variant in the PGC-1α gene was determined with the polymerase chain reaction amplification, Hpa II enzyme digestion, and gel electrophoresis. The Pro12Ala polymorphism of the PPAR-γ2 gene was determined by the polymerase chain reaction–single-strand conformation polymorphism analysis.

Results

The Pro12Pro genotype of the PPAR-γ2 gene predicted the conversion to diabetes in women in the acarbose group (odds ratio 2.89, 95% CI 1.20 to 6.96; p=0.018). The 482Ser allele of the PGC-1α gene had a significant interaction with the mode of treatment (p=0.012), and in the placebo group the 482Ser allele was associated with a 1.6-fold higher risk for type 2 diabetes compared to the Gly482Gly genotype (95% CI 1.06 to 2.33; p=0.023). Acarbose prevented the development of diabetes independently of the genotype of the PPAR-γ2 gene, but only the carriers of the 482Ser allele of the PGC-1α gene were responsive to acarbose treatment.

Conclusion/interpretation

We conclude that the Pro12Pro genotype of the PPAR-γ2 gene and the 482Ser allele of the PGC-1α gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.
Literatur
1.
Zurück zum Zitat Kahn CR, Vicent D, Doria A (1996) Genetics of non-insulin-dependent (type-II) diabetes mellitus. Annu Rev Med 47:509–531CrossRefPubMed Kahn CR, Vicent D, Doria A (1996) Genetics of non-insulin-dependent (type-II) diabetes mellitus. Annu Rev Med 47:509–531CrossRefPubMed
2.
Zurück zum Zitat Medici F, Hawa M, Ianari A, Pyke DA, Leslie RD (1999) Concordance rate for type II diabetes mellitus in monozygotic twins: actuarial analysis. Diabetologia 42:146–150CrossRefPubMed Medici F, Hawa M, Ianari A, Pyke DA, Leslie RD (1999) Concordance rate for type II diabetes mellitus in monozygotic twins: actuarial analysis. Diabetologia 42:146–150CrossRefPubMed
3.
Zurück zum Zitat Lehtovirta M, Kaprio J, Forsblom C, Eriksson J, Tuomilehto J, Groop L (2000) Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins. Diabetologia 43:285–293CrossRefPubMed Lehtovirta M, Kaprio J, Forsblom C, Eriksson J, Tuomilehto J, Groop L (2000) Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins. Diabetologia 43:285–293CrossRefPubMed
4.
Zurück zum Zitat Florez JC, Hirschhorn J, Altshuler D (2003) The inherited basis of diabetes mellitus: implications for the genetic analysis of complex traits. Annu Rev Genomics Hum Genet 4:257–291CrossRefPubMed Florez JC, Hirschhorn J, Altshuler D (2003) The inherited basis of diabetes mellitus: implications for the genetic analysis of complex traits. Annu Rev Genomics Hum Genet 4:257–291CrossRefPubMed
5.
Zurück zum Zitat Rosen ED, Spiegelman BM (2001) PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 276:37731–37734CrossRefPubMed Rosen ED, Spiegelman BM (2001) PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem 276:37731–37734CrossRefPubMed
6.
Zurück zum Zitat Gurnell M, Savage DB, Chatterjee VK, O’Rahilly S (2003) The metabolic syndrome: peroxisome proliferator-activated receptor gamma and its therapeutic modulation. J Clin Endocrinol Metab 88:2412–2421CrossRefPubMed Gurnell M, Savage DB, Chatterjee VK, O’Rahilly S (2003) The metabolic syndrome: peroxisome proliferator-activated receptor gamma and its therapeutic modulation. J Clin Endocrinol Metab 88:2412–2421CrossRefPubMed
8.
Zurück zum Zitat Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM (1994) mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 8:1224–1234PubMed Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM (1994) mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 8:1224–1234PubMed
9.
Zurück zum Zitat Tontonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79:1147–1156CrossRefPubMed Tontonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79:1147–1156CrossRefPubMed
10.
Zurück zum Zitat Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM (2000) Transcriptional regulation of adipogenesis. Genes Dev 14:1293–1307 Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM (2000) Transcriptional regulation of adipogenesis. Genes Dev 14:1293–1307
11.
Zurück zum Zitat Spiegelman BM (1998) PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 47:507–514PubMed Spiegelman BM (1998) PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 47:507–514PubMed
12.
Zurück zum Zitat Yamauchi T, Kamon J, Waki H et al. (2001) The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J Biol Chem 276:41245–41254CrossRefPubMed Yamauchi T, Kamon J, Waki H et al. (2001) The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J Biol Chem 276:41245–41254CrossRefPubMed
13.
14.
Zurück zum Zitat Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA (1995) An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 270:12953–12956CrossRefPubMed Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA (1995) An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 270:12953–12956CrossRefPubMed
15.
Zurück zum Zitat Tenenbaum A, Fisman EZ, Motro M (2003) Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). Cardiovasc Diabetol 2:14CrossRefPubMed Tenenbaum A, Fisman EZ, Motro M (2003) Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). Cardiovasc Diabetol 2:14CrossRefPubMed
16.
Zurück zum Zitat Yen CJ, Beamer BA, Negri C et al. (1997) Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun 241:270–274CrossRefPubMed Yen CJ, Beamer BA, Negri C et al. (1997) Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun 241:270–274CrossRefPubMed
17.
Zurück zum Zitat Deeb SS, Fajas L, Nemoto M et al. (1998) A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genet 20:284–287CrossRefPubMed Deeb SS, Fajas L, Nemoto M et al. (1998) A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genet 20:284–287CrossRefPubMed
18.
Zurück zum Zitat Hara K, Okada T, Tobe K et al. (2000) The Pro12Ala polymorphism in PPAR gamma2 may confer resistance to type 2 diabetes. Biochem Biophys Res Commun 271:212–216CrossRefPubMed Hara K, Okada T, Tobe K et al. (2000) The Pro12Ala polymorphism in PPAR gamma2 may confer resistance to type 2 diabetes. Biochem Biophys Res Commun 271:212–216CrossRefPubMed
19.
Zurück zum Zitat Altshuler D, Hirschhorn JN, Klannemark M et al. (2000) The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nature Genet 26:76–80CrossRefPubMed Altshuler D, Hirschhorn JN, Klannemark M et al. (2000) The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nature Genet 26:76–80CrossRefPubMed
20.
Zurück zum Zitat Mori H, Ikegami H, Kawaguchi Y et al. (2001) The Pro12→Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes 50:891–894PubMed Mori H, Ikegami H, Kawaguchi Y et al. (2001) The Pro12→Ala substitution in PPAR-gamma is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes 50:891–894PubMed
21.
Zurück zum Zitat Douglas JA, Erdos MR, Watanabe RM et al. (2001) The peroxisome proliferator-activated receptor-gamma2 Pro12A1a variant: association with type 2 diabetes and trait differences. Diabetes 50:886–890PubMed Douglas JA, Erdos MR, Watanabe RM et al. (2001) The peroxisome proliferator-activated receptor-gamma2 Pro12A1a variant: association with type 2 diabetes and trait differences. Diabetes 50:886–890PubMed
22.
Zurück zum Zitat Memisoglu A, Hu FB, Hankinson SE et al. (2003) Prospective study of the association between the proline to alanine codon 12 polymorphism in the PPARgamma gene and type 2 diabetes. Diabetes Care 26:2915–2917PubMed Memisoglu A, Hu FB, Hankinson SE et al. (2003) Prospective study of the association between the proline to alanine codon 12 polymorphism in the PPARgamma gene and type 2 diabetes. Diabetes Care 26:2915–2917PubMed
23.
Zurück zum Zitat Ringel J, Engeli S, Distler A, Sharma AM (1999) Pro12Ala missense mutation of the peroxisome proliferator activated receptor gamma and diabetes mellitus. Biochem Biophys Res Commun 254:450–453CrossRefPubMed Ringel J, Engeli S, Distler A, Sharma AM (1999) Pro12Ala missense mutation of the peroxisome proliferator activated receptor gamma and diabetes mellitus. Biochem Biophys Res Commun 254:450–453CrossRefPubMed
24.
Zurück zum Zitat Mancini FP, Vaccaro O, Sabatino L et al. (1999) Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma2 is not associated with type 2 diabetes. Diabetes 48:1466–1468PubMed Mancini FP, Vaccaro O, Sabatino L et al. (1999) Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma2 is not associated with type 2 diabetes. Diabetes 48:1466–1468PubMed
25.
Zurück zum Zitat Oh EY, Min KM, Chung JH et al. (2000) Significance of Pro12Ala mutation in peroxisome proliferator-activated receptor-gamma2 in Korean diabetic and obese subjects. J Clin Endocrinol Metab 85:1801–1804CrossRefPubMed Oh EY, Min KM, Chung JH et al. (2000) Significance of Pro12Ala mutation in peroxisome proliferator-activated receptor-gamma2 in Korean diabetic and obese subjects. J Clin Endocrinol Metab 85:1801–1804CrossRefPubMed
26.
Zurück zum Zitat Meirhaeghe A, Fajas L, Helbecque N et al. (2000) Impact of the Peroxisome Proliferator Activated Receptor gamma2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus. Int J Obes Relat Metab Disord 24:195–199CrossRefPubMed Meirhaeghe A, Fajas L, Helbecque N et al. (2000) Impact of the Peroxisome Proliferator Activated Receptor gamma2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus. Int J Obes Relat Metab Disord 24:195–199CrossRefPubMed
27.
Zurück zum Zitat Clement K, Hercberg S, Passinge B et al. (2000) The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes. Int J Obes Relat Metab Disord 24:391–393CrossRefPubMed Clement K, Hercberg S, Passinge B et al. (2000) The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes. Int J Obes Relat Metab Disord 24:391–393CrossRefPubMed
28.
Zurück zum Zitat Lei HH, Chen MH, Yang WS et al. (2000) Peroxisome proliferator-activated receptor gamma 2 Pro12Ala gene variant is strongly associated with larger body mass in the Taiwanese. Metabolism 49:1267–1270CrossRefPubMed Lei HH, Chen MH, Yang WS et al. (2000) Peroxisome proliferator-activated receptor gamma 2 Pro12Ala gene variant is strongly associated with larger body mass in the Taiwanese. Metabolism 49:1267–1270CrossRefPubMed
29.
Zurück zum Zitat Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839CrossRefPubMed Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839CrossRefPubMed
30.
Zurück zum Zitat Wu Z, Puigserver P, Andersson U et al. (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124CrossRefPubMed Wu Z, Puigserver P, Andersson U et al. (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124CrossRefPubMed
31.
Zurück zum Zitat Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24:78–90CrossRefPubMed Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24:78–90CrossRefPubMed
32.
Zurück zum Zitat Lin J, Wu H, Tarr PT et al. (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418:797–801CrossRefPubMed Lin J, Wu H, Tarr PT et al. (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418:797–801CrossRefPubMed
33.
Zurück zum Zitat Michael LF, Wu Z, Cheatham RB et al. (2001) Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc Natl Acad Sci USA 98:3820–3825CrossRefPubMed Michael LF, Wu Z, Cheatham RB et al. (2001) Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc Natl Acad Sci USA 98:3820–3825CrossRefPubMed
34.
Zurück zum Zitat Yoon JC, Puigserver P, Chen G et al. (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131–138CrossRefPubMed Yoon JC, Puigserver P, Chen G et al. (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131–138CrossRefPubMed
35.
Zurück zum Zitat Mootha VK, Lindgren CM, Eriksson KF et al. (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nature Genet 34:267–273CrossRefPubMed Mootha VK, Lindgren CM, Eriksson KF et al. (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nature Genet 34:267–273CrossRefPubMed
36.
Zurück zum Zitat Attie AD, Kendziorski CM (2003) PGC-1alpha at the crossroads of type 2 diabetes. Nature Genet 34:244–245CrossRefPubMed Attie AD, Kendziorski CM (2003) PGC-1alpha at the crossroads of type 2 diabetes. Nature Genet 34:244–245CrossRefPubMed
37.
Zurück zum Zitat Patti ME, Butte AJ, Crunkhorn S et al. (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100:8466–8471CrossRefPubMed Patti ME, Butte AJ, Crunkhorn S et al. (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100:8466–8471CrossRefPubMed
38.
Zurück zum Zitat Ek J, Andersen G, Urhammer SA, Gaede PH et al. (2001) Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus. Diabetologia 44:2220–2226CrossRefPubMed Ek J, Andersen G, Urhammer SA, Gaede PH et al. (2001) Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus. Diabetologia 44:2220–2226CrossRefPubMed
39.
Zurück zum Zitat Hara K, Tobe K, Okada T et al. (2002) A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes. Diabetologia 45:740–743CrossRefPubMed Hara K, Tobe K, Okada T et al. (2002) A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes. Diabetologia 45:740–743CrossRefPubMed
40.
Zurück zum Zitat Lacquemant C, Chikri M, Boutin P, Samson C, Froguel P (2002) No association between the G482S polymorphism of the proliferator-activated receptor- gamma coactivator-1 (PGC-1) gene and Type II diabetes in French Caucasians. Diabetologia 45:602–603; author reply 604CrossRefPubMed Lacquemant C, Chikri M, Boutin P, Samson C, Froguel P (2002) No association between the G482S polymorphism of the proliferator-activated receptor- gamma coactivator-1 (PGC-1) gene and Type II diabetes in French Caucasians. Diabetologia 45:602–603; author reply 604CrossRefPubMed
41.
Zurück zum Zitat Muller YL, Bogardus C, Pedersen O, Baier L (2003) A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians. Diabetes 52:895–898PubMed Muller YL, Bogardus C, Pedersen O, Baier L (2003) A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians. Diabetes 52:895–898PubMed
42.
Zurück zum Zitat Chiasson JL, Gomis R, Hanefeld M, Josse RG, Karasik A, Laakso M (1998) The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus. Diabetes Care 21:1720–1725PubMed Chiasson JL, Gomis R, Hanefeld M, Josse RG, Karasik A, Laakso M (1998) The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus. Diabetes Care 21:1720–1725PubMed
43.
Zurück zum Zitat World Health Organization (1985) Diabetes mellitus. WHO, Geneva, pp 10–11 World Health Organization (1985) Diabetes mellitus. WHO, Geneva, pp 10–11
44.
Zurück zum Zitat Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M (2002) Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359:2072–2077CrossRefPubMed Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M (2002) Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359:2072–2077CrossRefPubMed
45.
Zurück zum Zitat Albareda M, Rodriguez-Espinosa J, Murugo M, Leiva A de, Corcoy R (2000) Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test. Diabetologia 43:1507–1511CrossRefPubMed Albareda M, Rodriguez-Espinosa J, Murugo M, Leiva A de, Corcoy R (2000) Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test. Diabetologia 43:1507–1511CrossRefPubMed
46.
Zurück zum Zitat Kubota N, Terauchi Y, Miki H et al. (1999) PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 4:597–609CrossRefPubMed Kubota N, Terauchi Y, Miki H et al. (1999) PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 4:597–609CrossRefPubMed
47.
Zurück zum Zitat Stefan N, Fritsche A, Haring H, Stumvoll M (2001) Effect of experimental elevation of free fatty acids on insulin secretion and insulin sensitivity in healthy carriers of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene. Diabetes 50:1143–1148PubMed Stefan N, Fritsche A, Haring H, Stumvoll M (2001) Effect of experimental elevation of free fatty acids on insulin secretion and insulin sensitivity in healthy carriers of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene. Diabetes 50:1143–1148PubMed
48.
Zurück zum Zitat Lindi VI, Uusitupa MI, Lindström J, et al. for the Finnish Diabetes Prevention Study Group (2002) Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes 51:2581–2586PubMed Lindi VI, Uusitupa MI, Lindström J, et al. for the Finnish Diabetes Prevention Study Group (2002) Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes 51:2581–2586PubMed
49.
Zurück zum Zitat Pratley RE, Thompson DB, Prochazka M et al. (1998) An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians. J Clin Invest 101:1757–1764PubMed Pratley RE, Thompson DB, Prochazka M et al. (1998) An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians. J Clin Invest 101:1757–1764PubMed
50.
Zurück zum Zitat Esterbauer H, Oberkofler H, Krempler F, Patsch W (1999) Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression. Genomics 62:98–102CrossRefPubMed Esterbauer H, Oberkofler H, Krempler F, Patsch W (1999) Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression. Genomics 62:98–102CrossRefPubMed
51.
Zurück zum Zitat Hammarstedt A, Jansson PA, Wesslau C, Yang X, Smith U (2003) Reduced expression of PGC-1 and insulin-signaling molecules in adipose tissue is associated with insulin resistance. Biochem Biophys Res Commun 301:578–582CrossRefPubMed Hammarstedt A, Jansson PA, Wesslau C, Yang X, Smith U (2003) Reduced expression of PGC-1 and insulin-signaling molecules in adipose tissue is associated with insulin resistance. Biochem Biophys Res Commun 301:578–582CrossRefPubMed
Metadaten
Titel
Common polymorphisms of the PPAR-γ2 (Pro12Ala) and PGC-1α (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial
verfasst von
L. Andrulionytè
J. Zacharova
J.-L. Chiasson
M. Laakso
for the STOP-NIDDM Study Group
Publikationsdatum
01.12.2004
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 12/2004
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1577-2

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