C. Ethnicity and . Disease, The incidence of myocardial infarction in white, South Asian, and Afro-Caribbean patients with type 2 diabetes (U.K. Prospective Diabetes Study 32) Diabetes Care, pp.1271-1277, 1998.

B. Ahren, Autonomic regulation of islet hormone secretion - Implications for health and disease, Diabetologia, vol.43, issue.4, pp.393-410, 2000.
DOI : 10.1007/s001250051322

K. Alberti and P. Zimmet, Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications Part 1: Diagnosis and Classification of Diabetes Mellitus, World Health Transplantation, issue.2, 1999.

K. Alberti, R. Eckel, S. Grundy, P. Zimmet, and J. Cleeman, Harmonizing the Metabolic Syndrome: A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity, Circulation, vol.120, issue.16, pp.1640-1645, 2009.
DOI : 10.1161/CIRCULATIONAHA.109.192644

K. Alberti and P. Zimmet, Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO Consultation, Diabetic Medicine, vol.15, issue.7, pp.539-553, 1998.
DOI : 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S

K. Alitalo and P. Carmeliet, Molecular mechanisms of lymphangiogenesis in health and disease, Cancer Cell, vol.1, issue.3, pp.219-227, 2002.
DOI : 10.1016/S1535-6108(02)00051-X

D. Altshuler, J. Hirschhorn, M. Klannemark, C. Lindgren, and M. Vohl, The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes, Nat.Genet, vol.26, pp.76-80, 2000.

F. Archambeaud, J. Attali, X. Bertagna, J. Bringer, and C. Boitard, Mesure de l'insulinosécrétion (I) Méthodes d'évaluation de l'insulinosécrétion dans les études de population, 2001.

A. Arimura and S. Shioda, Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and Its Receptors: Neuroendocrine and Endocrine Interaction, Frontiers in Neuroendocrinology, vol.16, issue.1, pp.53-88, 1995.
DOI : 10.1006/frne.1995.1003

H. Aschard, J. Chen, M. Cornelis, L. Chibnik, and E. Karlson, Inclusion of gene-gene and geneenvironment interactions unlikely to dramatically improve risk prediction for complex diseases

M. Asfari, D. Janjic, P. Meda, G. Li, and P. Halban, Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines, Endocrinology, vol.130, pp.167-178, 1992.

A. Avignon, P. Barbe, A. Basdevant, J. Bresson, and C. C. , Diabète de type II Physiopathologie, Cah.Nutr.Diét, vol.36, issue.2, pp.1-163, 2001.

S. Banerji, J. Ni, S. Wang, S. Clasper, and J. Su, LYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-specific Receptor for Hyaluronan, The Journal of Cell Biology, vol.8, issue.4, pp.789-801, 1999.
DOI : 10.1002/jcb.240480111

A. Barker, C. Langenberg, and N. Wareham, Genetic determinants of glucose homeostasis, Best Practice & Research Clinical Endocrinology & Metabolism, vol.26, issue.2
DOI : 10.1016/j.beem.2011.12.002

A. Barker, S. Sharp, N. Timpson, N. Bouatia-naji, and N. Warrington, Association of Genetic Loci With Glucose Levels in Childhood and Adolescence: A Meta-Analysis of Over 6,000 Children, Diabetes, vol.60, issue.6, pp.1805-1812, 2011.
DOI : 10.2337/db10-1575

D. Barker, J. Eriksson, T. Forsen, and O. C. , Fetal origins of adult disease: strength of effects and biological basis, International Journal of Epidemiology, vol.31, issue.6, pp.1235-1239, 2002.
DOI : 10.1093/ije/31.6.1235

N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich, Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species, Physiological Reviews, vol.89, issue.1, pp.27-71, 2009.
DOI : 10.1152/physrev.00014.2008

S. Baxter, D. Cheung, P. Bocangel, H. Kim, and K. Herbert, Regulation of the lymphatic endothelial cell cycle by the PROX1 homeodomain protein, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol.1813, issue.1, pp.201-212, 2011.
DOI : 10.1016/j.bbamcr.2010.10.015

J. Beckman, M. Creager, and P. Libby, Diabetes and Atherosclerosis, JAMA, vol.287, issue.19, pp.2570-2581, 2002.
DOI : 10.1001/jama.287.19.2570

J. Berger and D. Moller, The Mechanisms of Action of PPARs, Annual Review of Medicine, vol.53, issue.1, pp.409-435, 2002.
DOI : 10.1146/annurev.med.53.082901.104018

S. Bhasin, L. Woodhouse, R. Casaburi, A. Singh, and D. Bhasin, Testosterone dose-response relationships in healthy young men, Am.J.Physiol Endocrinol.Metab, vol.281, pp.1172-1181, 2001.

X. Bi, A. Kajava, T. Jones, Z. Demidenko, and M. Mortin, The Carboxy Terminus of Prospero Regulates Its Subcellular Localization, Molecular and Cellular Biology, vol.23, issue.3, pp.1014-1024, 2003.
DOI : 10.1128/MCB.23.3.1014-1024.2003

L. Billings and J. Florez, The genetics of type 2 diabetes: what have we learned from GWAS?, Annals of the New York Academy of Sciences, vol.461, issue.Suppl 1, pp.59-77, 2010.
DOI : 10.1111/j.1749-6632.2010.05838.x

E. Blaak, Sex differences in the control of glucose homeostasis, Current Opinion in Clinical Nutrition and Metabolic Care, vol.11, issue.4, pp.500-504, 2008.
DOI : 10.1097/MCO.0b013e32830467d3

J. Bland and D. Altman, Statistics notes: Multiple significance tests: the Bonferroni method, BMJ, vol.310, issue.6973, p.170, 1995.
DOI : 10.1136/bmj.310.6973.170

N. Bouatia-naji, A. Bonnefond, C. Cavalcanti-proenca, T. Sparso, and J. Holmkvist, A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk, Nature Genetics, vol.49, issue.1, pp.89-94, 2009.
DOI : 10.1038/ng2088

N. Bouatia-naji, G. Rocheleau, L. Van-lommel, K. Lemaire, and F. Schuit, A Polymorphism Within the G6PC2 Gene Is Associated with Fasting Plasma Glucose Levels, Science, vol.320, issue.5879, pp.1085-1088, 2008.
DOI : 10.1126/science.1156849

P. Boyle, Diabetes Mellitus and Macrovascular Disease: Mechanisms and Mediators, The American Journal of Medicine, vol.120, issue.9, pp.12-17, 2007.
DOI : 10.1016/j.amjmed.2007.07.003

M. Brissova, M. Shiota, W. Nicholson, M. Gannon, and S. Knobel, Reduction in Pancreatic Transcription Factor PDX-1 Impairs Glucose-stimulated Insulin Secretion, Journal of Biological Chemistry, vol.277, issue.13, pp.11225-11232, 2002.
DOI : 10.1074/jbc.M111272200

M. Brownlee, Biochemistry and molecular cell biology of diabetic complications, Nature, vol.414, issue.6865, pp.813-820, 2001.
DOI : 10.1038/414813a

T. Buchanan, A. Xiang, and K. Page, Gestational diabetes mellitus: risks and management during and after pregnancy, Nature Reviews Endocrinology, vol.33, issue.11, 2012.
DOI : 10.1038/nrendo.2012.96

M. Burg, Molecular basis of osmotic regulation, Am.J.Physiol, vol.268, pp.983-996, 1995.

Z. Burke and G. Oliver, Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm, Mechanisms of Development, vol.118, issue.1-2, pp.147-155, 2002.
DOI : 10.1016/S0925-4773(02)00240-X

S. Bustin, Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays, Journal of Molecular Endocrinology, vol.25, issue.2, pp.169-193, 2000.
DOI : 10.1677/jme.0.0250169

S. Cauchi, D. Meyre, E. Durand, C. Proenca, and M. Marre, Post Genome-Wide Association Studies of Novel Genes Associated with Type 2 Diabetes Show Gene-Gene Interaction and High Predictive Value, PLoS ONE, vol.21, issue.5, p.2031, 2008.
DOI : 10.1371/journal.pone.0002031.s003

P. Chamnan, R. Simmons, N. Forouhi, R. Luben, and K. Khaw, Incidence of Type 2 Diabetes Using Proposed HbA1c Diagnostic Criteria in the European Prospective Investigation of Cancer-Norfolk Cohort: Implications for preventive strategies, Diabetes Care, vol.34, issue.4, pp.950-956, 2011.
DOI : 10.2337/dc09-2326

C. Chan, ??-Cell stimulus???secretion coupling defects in rodent models of obesity, Canadian Journal of Physiology and Pharmacology, vol.73, issue.10, pp.1414-1424, 1995.
DOI : 10.1139/y95-197

J. Chan, V. Malik, W. Jia, T. Kadowaki, and C. Yajnik, Diabetes in Asia, JAMA, vol.301, issue.20, pp.2129-2140, 2009.
DOI : 10.1001/jama.2009.726

S. Chan, C. Perrett, and N. Morgan, Differential Expression of ??2-Adrenoceptor Subtypes in Purified Rat Pancreatic Islet A- and B-Cells, Cellular Signalling, vol.9, issue.1, pp.71-78, 1997.
DOI : 10.1016/S0898-6568(96)00096-4

A. Charest-marcotte, C. Dufour, B. Wilson, A. Tremblay, and L. Eichner, The homeobox protein Prox1 is a negative modulator of ERR??/PGC-1?? bioenergetic functions, Genes & Development, vol.24, issue.6, pp.537-542, 2010.
DOI : 10.1101/gad.1871610

M. Choi, U. Scholl, J. W. Liu, T. Tikhonova, and I. , Genetic diagnosis by whole exome capture and massively parallel DNA sequencing, Proceedings of the National Academy of Sciences, vol.106, issue.45, pp.19096-19101, 2009.
DOI : 10.1073/pnas.0910672106

A. Clark, C. Wells, I. Buley, J. Cruickshank, and R. Vanhegan, Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes, Diabetes Res, vol.9, pp.151-159, 1988.

D. Clayton and P. Mckeigue, Epidemiological methods for studying genes and environmental factors in complex diseases, The Lancet, vol.358, issue.9290, pp.1356-1360, 2001.
DOI : 10.1016/S0140-6736(01)06418-2

T. Cole, M. Bellizzi, K. Flegal, and W. Dietz, Establishing a standard definition for child overweight and obesity worldwide: international survey, BMJ, vol.320, issue.7244, pp.1240-1243, 2000.
DOI : 10.1136/bmj.320.7244.1240

T. Cook, F. Pichaud, R. Sonneville, D. Papatsenko, and C. Desplan, Distinction between Color Photoreceptor Cell Fates Is Controlled by Prospero in Drosophila, Developmental Cell, vol.4, issue.6, pp.853-864, 2003.
DOI : 10.1016/S1534-5807(03)00156-4

C. Cueille and J. Garel, RAMP et r??cepteurs coupl??s aux prot??ines G, m??decine/sciences, vol.20, issue.8-9, pp.773-778, 2004.
DOI : 10.1051/medsci/2004208-9773

D. Adamo, E. Caprio, and S. , Type 2 Diabetes in Youth: Epidemiology and Pathophysiology, Diabetes Care, vol.34, issue.Supplement_2, pp.161-165, 2011.
DOI : 10.2337/dc11-s212

D. Dabelea, R. Bell, D. Agostino, R. , J. Imperatore et al., Incidence of diabetes in youth in the United States, JAMA, vol.297, pp.2716-2724, 2007.

T. Davis, Ethnic diversity in Type 2 diabetes, Diabetic Medicine, vol.6, issue.2, pp.52-56, 2008.
DOI : 10.1111/j.1464-5491.2008.02499.x

D. Martino, M. Alesci, S. Chrousos, G. Kino, and T. , Interaction of the Glucocorticoid Receptor and the Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII): Implications for the Actions of Glucocorticoids on Glucose, Lipoprotein, and Xenobiotic Metabolism, Annals of the New York Academy of Sciences, vol.58, issue.1, pp.72-85, 2004.
DOI : 10.1196/annals.1321.006

. Decode-study and . Group, Age- and Sex-Specific Prevalences of Diabetes and Impaired Glucose Regulation in 13 European Cohorts, Diabetes Care, vol.26, issue.1, pp.61-69, 2003.
DOI : 10.2337/diacare.26.1.61

K. Docherty and A. Clark, Nutrient regulation of insulin gene expression, FASEB J, vol.8, pp.20-27, 1994.

A. Dotevall, A. Rosengren, M. Bartnik, K. Malmberg, and J. Ohrvik, Sex-related aspects on abnormal glucose regulation in patients with coronary artery disease, European Heart Journal, vol.28, issue.3, pp.310-315, 2007.
DOI : 10.1093/eurheartj/ehl458

M. Doyle and J. Egan, Mechanisms of action of glucagon-like peptide 1 in the pancreas, Pharmacology & Therapeutics, vol.113, issue.3, pp.546-593, 2007.
DOI : 10.1016/j.pharmthera.2006.11.007

R. Dudek, High-yield embryology, 2007.

C. Dufour, M. Levasseur, N. Pham, L. Eichner, and B. Wilson, Genomic Convergence among ERR??, PROX1, and BMAL1 in the Control of Metabolic Clock Outputs, PLoS Genetics, vol.99, issue.6, p.1002143, 2011.
DOI : 10.1371/journal.pgen.1002143.s013

J. Dupuis, C. Langenberg, I. Prokopenko, R. Saxena, and N. Soranzo, New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk, Nature Genetics, vol.49, issue.2, pp.105-116, 2010.
DOI : 10.1038/ng.520

M. Dyer, F. Livesey, C. Cepko, and G. Oliver, Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina, Nature Genetics, vol.34, issue.1, pp.53-58, 2003.
DOI : 10.1038/ng1144

S. Efrat, Regulation of Insulin Secretion: Insights from Engineered ??-cell Lines, Annals of the New York Academy of Sciences, vol.100, issue.Suppl. 3, pp.88-96, 2004.
DOI : 10.1196/annals.1294.009

E. Eichler, J. Flint, G. Gibson, A. Kong, and S. Leal, Missing heritability and strategies for finding the underlying causes of complex disease, Nature Reviews Genetics, vol.90, issue.6, pp.446-450, 2010.
DOI : 10.1038/nrg2809

A. Elayat, M. Naggar, and M. Tahir, An immunocytochemical and morphometric study of the rat pancreatic islets, J.Anat, vol.186, pp.629-637, 1995.

T. Elsir, A. Smits, M. Lindstrom, and M. Nister, Transcription factor PROX1: its role in development and cancer, Cancer and Metastasis Reviews, vol.359, issue.2, pp.793-805, 2012.
DOI : 10.1007/s10555-012-9390-8

A. Fagot-campagna, S. Fosse, C. Roudier, I. Romon, and A. Penfornis, Caractéristiques, risque vasculaire et complications chez les personnes diabétiques en France métropolitaine : d'importantes évolutions entre Entred, BEH, pp.42-43, 2001.

S. Fajans, J. Floyd, and J. , Fasting Hypoglycemia in Adults, New England Journal of Medicine, vol.294, issue.14, pp.766-772, 1976.
DOI : 10.1056/NEJM197604012941408

R. Farese, Insulin-Sensitive Phospholipid Signaling Systems and Glucose Transport: An Update, Experimental Biology and Medicine, vol.213, issue.1
DOI : 10.3181/00379727-213-44030

L. Farilla, H. Hui, C. Bertolotto, E. Kang, and A. Bulotta, Glucagon-Like Peptide-1 Promotes Islet Cell Growth and Inhibits Apoptosis in Zucker Diabetic Rats, Endocrinology, vol.143, issue.11, pp.4397-4408, 2002.
DOI : 10.1210/en.2002-220405

E. Fisher, H. Boeing, A. Fritsche, F. Doering, and H. Joost, Whole-grain consumption and transcription factor-7-like 2 ( TCF7L2) rs7903146: gene???diet interaction in modulating type 2 diabetes risk, British Journal of Nutrition, vol.215, issue.04, pp.478-481, 2009.
DOI : 10.1159/000012789

J. Flint and T. Mackay, Genetic architecture of quantitative traits in mice, flies, and humans, Genome Research, vol.19, issue.5, pp.723-733, 2009.
DOI : 10.1101/gr.086660.108

J. Florez, Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: Where are the insulin resistance genes?, Diabetologia, vol.8, issue.7, pp.1100-1110, 2008.
DOI : 10.1007/s00125-008-1025-9

D. Fong, L. Aiello, F. Ferris, I. Klein, and R. Diabetic, Diabetic Retinopathy, Diabetes Care, vol.27, issue.10, pp.2540-2553, 2004.
DOI : 10.2337/diacare.27.10.2540

E. Ford, C. Li, and N. Sattar, Metabolic Syndrome and Incident Diabetes: Current state of the evidence, Diabetes Care, vol.31, issue.9, pp.1898-1904, 2008.
DOI : 10.2337/dc08-0423

T. Forst, D. L. Tour, D. Kunt, T. Pfutzner, A. Goitom et al., Effects of proinsulin C-peptide on nitric oxide, microvascular blood flow and erythrocyte Na+,K+-ATPase activity in diabetes mellitus type I, Clinical Science, vol.98, issue.3, pp.283-290, 2000.
DOI : 10.1042/cs0980283

M. Fowler, Microvascular and Macrovascular Complications of Diabetes, Clinical Diabetes, vol.29, issue.3, pp.116-122, 2011.
DOI : 10.2337/diaclin.29.3.116

M. Francois, A. Caprini, B. Hosking, F. Orsenigo, and D. Wilhelm, Sox18 induces development of the lymphatic vasculature in mice, Nature, vol.141, issue.7222, pp.643-647, 2008.
DOI : 10.1038/nature07391

S. Furihata, T. Ito, and N. Kamatani, Test of Association Between Haplotypes and Phenotypes in Case-Control Studies: Examination of Validity of the Application of an Algorithm for Samples From Cohort or Clinical Trials to Case-Control Samples Using Simulated and Real Data, Genetics, vol.174, issue.3, pp.1505-1516, 2006.
DOI : 10.1534/genetics.105.054452

M. Gallagher, R. Goland, and C. Greenbaum, Making progress: preserving beta cells in type 1 diabetes, Annals of the New York Academy of Sciences, vol.328, issue.1
DOI : 10.1111/j.1749-6632.2011.06321.x

E. Galsgaard, F. Gouilleux, B. Groner, P. Serup, and J. Nielsen, Identification of a growth hormoneresponsive STAT5-binding element in the rat insulin 1 gene, Mol.Endocrinol, vol.10, pp.652-660, 1996.

W. J. Gauderman and J. Morrison, QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies, 2006.

S. Genuth, K. Alberti, P. Bennett, J. Buse, and R. Defronzo, Follow-up report on the diagnosis of diabetes mellitus, Diabetes Care, vol.26, pp.3160-3167, 2003.

U. Gibson, C. Heid, and P. Williams, A novel method for real time quantitative RT-PCR., Genome Research, vol.6, issue.10, pp.995-1001, 1996.
DOI : 10.1101/gr.6.10.995

E. Gilbert and D. Liu, Epigenetics: The missing link to understanding ??-cell dysfunction in the pathogenesis of type 2 diabetes, Epigenetics, vol.153, issue.8, pp.841-852, 2012.
DOI : 10.1016/j.cmet.2011.02.012

J. Girard, Contribution of free fatty acids to impairment of insulin secretion and action. mechanism of beta-cell lipotoxicity, Med.Sci.(Paris), vol.21, pp.19-25, 2005.

A. Gloyn, M. Weedon, K. Owen, M. Turner, and B. Knight, Large-Scale Association Studies of Variants in Genes Encoding the Pancreatic ??-Cell KATP Channel Subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) Confirm That the KCNJ11 E23K Variant Is Associated With Type 2 Diabetes, Diabetes, vol.52, issue.2, pp.568-572, 2003.
DOI : 10.2337/diabetes.52.2.568

S. Greenland, Basic problems in interaction assessment, Environmental Health Perspectives, vol.101, issue.Suppl 4, pp.59-66, 1993.
DOI : 10.1289/ehp.93101s459

M. Harris, W. Hadden, W. Knowler, and P. Bennett, Prevalence of Diabetes and Impaired Glucose Tolerance and Plasma Glucose Levels in U.S. Population Aged 20-74 Yr, Diabetes, vol.36, issue.4, pp.523-534, 1987.
DOI : 10.2337/diab.36.4.523

N. Harvey, R. Srinivasan, M. Dillard, N. Johnson, and M. Witte, Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity, Nature Genetics, vol.221, issue.10, pp.1072-1081, 2005.
DOI : 10.1053/j.gastro.2004.04.007

B. Hassan, L. Li, K. Bremer, W. Chang, and J. Pinsonneault, Prospero is a panneural transcription factor that modulates homeodomain protein activity, Proceedings of the National Academy of Sciences, vol.94, issue.20, pp.10991-10996, 1997.
DOI : 10.1073/pnas.94.20.10991

A. Haupt, C. Thamer, J. Machann, K. Kirchhoff, and N. Stefan, Gene on Whole Body Fat Distribution, Ectopic Fat, and Weight Loss, Obesity, vol.18, issue.8, pp.1969-1972, 2008.
DOI : 10.1038/oby.2008.283

T. Hillier, A. Fagot-campagna, E. Eschwege, S. Vol, and M. Cailleau, Weight change and changes in the metabolic syndrome as the French population moves towards overweight: The D.E.S.I.R. Cohort, International Journal of Epidemiology, vol.35, issue.1
DOI : 10.1093/ije/dyi281

URL : https://hal.archives-ouvertes.fr/inserm-00128713

C. Hills and N. Brunskill, Cellular and physiological effects of C-peptide, Clinical Science, vol.116, issue.7, pp.565-574, 2009.
DOI : 10.1042/CS20080441

Y. Hong, N. Harvey, Y. Noh, V. Schacht, and S. Hirakawa, Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate, Developmental Dynamics, vol.35, issue.3, pp.351-357, 2002.
DOI : 10.1002/dvdy.10163

Y. Horikawa, N. Oda, N. Cox, X. Li, and M. Orho-melander, Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus, Nature Genetics, vol.11, issue.2, pp.163-175, 2000.
DOI : 10.1086/301592

G. Hotamisligil, D. Murray, L. Choy, and B. Spiegelman, Tumor necrosis factor alpha inhibits signaling from the insulin receptor., Proceedings of the National Academy of Sciences, vol.91, issue.11, pp.4854-4858, 1994.
DOI : 10.1073/pnas.91.11.4854

B. Howie, P. Donnelly, and J. Marchini, A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies, PLoS Genetics, vol.84, issue.6, p.1000529, 2009.
DOI : 10.1371/journal.pgen.1000529.s004

M. Imamura and S. Maeda, Genetics of type 2 diabetes: the GWAS era and future perspectives [Review], Endocrine Journal, vol.58, issue.9, pp.723-739, 2011.
DOI : 10.1507/endocrj.EJ11-0113

H. International and . Consortium, The International HapMap Project, Nature, vol.426, pp.789-796, 2003.

K. Jayapal, S. Sui, R. Philp, Y. Kok, and M. Yap, Multitagging Proteomic Strategy to Estimate Protein Turnover Rates in Dynamic Systems, Journal of Proteome Research, vol.9, issue.5, pp.2087-2097, 2010.
DOI : 10.1021/pr9007738

M. Kaijser, A. Bonamy, O. Akre, S. Cnattingius, and F. Granath, Perinatal Risk Factors for Diabetes in Later Life, Diabetes, vol.58, issue.3, pp.523-526, 2009.
DOI : 10.2337/db08-0558

A. Kaipainen, J. Korhonen, T. Mustonen, V. Van-hinsbergh, and G. Fang, Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development., Proceedings of the National Academy of Sciences, vol.92, issue.8
DOI : 10.1073/pnas.92.8.3566

V. Kaltezioti, G. Kouroupi, M. Oikonomaki, E. Mantouvalou, and A. Stergiopoulos, Prox1 Regulates the Notch1-Mediated Inhibition of Neurogenesis, PLoS Biology, vol.7, issue.12, p.1000565, 2010.
DOI : 10.1371/journal.pbio.1000565.s012

A. Kamiya, S. Kakinuma, M. Onodera, A. Miyajima, and H. Nakauchi, Prospero-related homeobox 1 and liver receptor homolog 1 coordinately regulate long-term proliferation of murine fetal hepatoblasts, Hepatology, vol.19, issue.1, pp.252-264, 2008.
DOI : 10.1002/hep.22303

H. Kampfer, U. Kalina, H. Muhl, J. Pfeilschifter, and S. Frank, Counterregulation of Interleukin-18 mRNA and Protein Expression During Cutaneous Wound Repair in Mice, Journal of Investigative Dermatology, vol.113, issue.3, pp.369-374, 1999.
DOI : 10.1046/j.1523-1747.1999.00704.x

O. Karalay, K. Doberauer, K. Vadodaria, M. Knobloch, and L. Berti, Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis, Proceedings of the National Academy of Sciences, vol.108, issue.14, pp.5807-5812, 2011.
DOI : 10.1073/pnas.1013456108

S. Karsten, L. Kudo, and D. Geschwind, Microarray Platforms: Introduction and Application to Neurobiology, Int.Rev.Neurobiol, vol.60, pp.1-23, 2004.
DOI : 10.1016/S0074-7742(04)60001-8

T. Kawai, H. Hirose, Y. Seto, H. Fujita, and H. Fujita, Troglitazone ameliorates lipotoxicity in the beta cell line INS-1 expressing PPAR gamma, Diabetes Research and Clinical Practice, vol.56, issue.2, pp.83-92, 2002.
DOI : 10.1016/S0168-8227(01)00367-9

P. Kearney, L. Blackwell, R. Collins, A. Keech, and J. Simes, Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis, Lancet, vol.371, pp.117-125, 2008.

F. Khan, P. Goforth, M. Zhang, and L. Satin, Insulin Activates ATP-Sensitive K+ Channels in Pancreatic ??-Cells Through a Phosphatidylinositol 3-Kinase-Dependent Pathway, Diabetes, vol.50, issue.10, pp.2192-2198, 2001.
DOI : 10.2337/diabetes.50.10.2192

H. Kim and Y. Ahn, Role of Peroxisome Proliferator-Activated Receptor-?? in the Glucose-Sensing Apparatus of Liver and ??-Cells, Diabetes, vol.53, issue.Supplement 1, pp.60-65, 2004.
DOI : 10.2337/diabetes.53.2007.S60

A. Kitabchi, G. Umpierrez, M. Murphy, and R. Kreisberg, Hyperglycemic Crises in Adult Patients With Diabetes: A consensus statement from the American Diabetes Association, Diabetes Care, vol.29, issue.12, pp.2739-2748, 2006.
DOI : 10.2337/dc06-9916

A. Kong, V. Steinthorsdottir, G. Masson, G. Thorleifsson, and P. Sulem, Parental origin of sequence variants associated with complex diseases, Nature, vol.19, issue.7275, pp.868-874, 2009.
DOI : 10.1038/nature08625

W. Koppenol, The Haber-Weiss cycle ??? 70 years later, Redox Report, vol.245, issue.4, pp.229-234, 2001.
DOI : 10.1073/pnas.91.26.12365

A. Laerm, P. Helmbold, M. Goldberg, R. Dammann, and H. Holzhausen, Prospero-related homeobox 1 (PROX1) is frequently inactivated by genomic deletions and epigenetic silencing in carcinomas of the bilary system, Journal of Hepatology, vol.46, issue.1, pp.89-97, 2007.
DOI : 10.1016/j.jhep.2006.07.033

A. Lavado, O. Lagutin, L. Chow, S. Baker, and G. Oliver, Prox1 Is Required for Granule Cell Maturation and Intermediate Progenitor Maintenance During Brain Neurogenesis, PLoS Biology, vol.255, issue.8, p.1000460, 2010.
DOI : 10.1371/journal.pbio.1000460.s012

S. Lee, J. Kang, J. Yoo, S. Ganesan, and S. Cook, Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate, Blood, vol.113, issue.8, pp.1856-1859, 2009.
DOI : 10.1182/blood-2008-03-145789

I. Leibiger, B. Leibiger, and P. Berggren, Insulin feedback action on pancreatic ??-cell function, FEBS Letters, vol.28, issue.1-2, pp.1-6, 2002.
DOI : 10.1016/S0014-5793(02)03627-X

J. Lengler, E. Krausz, S. Tomarev, A. Prescott, and R. Quinlan, Antagonistic action of Six3 and Prox1 at the gamma-crystallin promoter, Nucleic Acids Research, vol.29, issue.2, pp.515-526, 2001.
DOI : 10.1093/nar/29.2.515

C. Lewis, A. Clark, S. Ashcroft, G. Cooper, and J. Morris, Calcitonin gene-related peptide and somatostatin inhibit insulin release from individual rat B cells, Molecular and Cellular Endocrinology, vol.57, issue.1-2, pp.41-49, 1988.
DOI : 10.1016/0303-7207(88)90030-5

P. Light, M. Fox, J. Riedel, M. Wheeler, and M. , Glucagon-Like Peptide-1 Inhibits Pancreatic ATP-Sensitive Potassium Channels via a Protein Kinase A- and ADP-Dependent Mechanism, Molecular Endocrinology, vol.16, issue.9, pp.2135-2144, 2002.
DOI : 10.1210/me.2002-0084

Y. Liu, W. Gao, H. Teh, J. Tan, and W. Chan, Prox1 Is a Novel Coregulator of Ff1b and Is Involved in the Embryonic Development of the Zebra Fish Interrenal Primordium, Molecular and Cellular Biology, vol.23, issue.20, pp.7243-7255, 2003.
DOI : 10.1128/MCB.23.20.7243-7255.2003

I. Lonnstedt and T. Britton, Hierarchical Bayes models for cDNA microarray gene expression, Biostatistics, vol.6, issue.2, pp.279-291, 2005.
DOI : 10.1093/biostatistics/kxi009

P. Luppi, V. Cifarelli, H. Tse, J. Piganelli, and M. Trucco, Human C-peptide antagonises high glucose-induced endothelial dysfunction through the nuclear factor-??B pathway, Diabetologia, vol.285, issue.Suppl 1, pp.1534-1543, 2008.
DOI : 10.1007/s00125-008-1032-x

I. Mackay, K. Arden, and A. Nitsche, Real-time PCR in virology, Nucleic Acids Research, vol.30, issue.6, pp.1292-1305, 2002.
DOI : 10.1093/nar/30.6.1292

C. Magnan and A. Ktorza, Production et s??cr??tion de l'insuline par la cellule ?? pancr??atique, EMC - Endocrinologie, vol.2, issue.4, pp.241-264, 2005.
DOI : 10.1016/j.emcend.2005.07.001

N. Marx, D. Walcher, C. Raichle, M. Aleksic, and H. Bach, C-Peptide Colocalizes with Macrophages in Early Arteriosclerotic Lesions of Diabetic Subjects and Induces Monocyte Chemotaxis In Vitro, Arteriosclerosis, Thrombosis, and Vascular Biology, vol.24, issue.3, pp.540-545, 2004.
DOI : 10.1161/01.ATV.0000116027.81513.68

D. Matthews, J. Hosker, A. Rudenski, B. Naylor, and D. Treacher, Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in man, Diabetologia, vol.92, issue.7, pp.412-419, 1985.
DOI : 10.1007/BF00280883

A. Matveyenko and P. Butler, Relationship between ??-cell mass and diabetes onset, Diabetes, Obesity and Metabolism, vol.23, issue.Suppl. 1, pp.23-31, 2008.
DOI : 10.1111/j.1463-1326.2008.00939.x

N. Mauras, V. Hayes, S. Welch, A. Rini, and K. Helgeson, Testosterone Deficiency in Young Men: Marked Alterations in Whole Body Protein Kinetics, Strength, and Adiposity, Journal of Clinical Endocrinology & Metabolism, vol.83, issue.6, pp.1886-1892, 1998.
DOI : 10.1210/jc.83.6.1886

J. Mcgarry, Banting Lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes, Diabetes, vol.51, issue.1, pp.7-18, 2002.
DOI : 10.2337/diabetes.51.1.7

J. Meyer, J. Froelich, G. Reid, W. Karunarathne, and D. Spence, Metal-activated C-peptide facilitates glucose clearance and the release of a nitric oxide stimulus via the GLUT1 transporter, Diabetologia, vol.445, issue.1, pp.175-182, 2008.
DOI : 10.1007/s00125-007-0853-3

P. Miles, O. Romeo, K. Higo, A. Cohen, and K. Rafaat, TNF-alpha-induced insulin resistance in vivo and its prevention by troglitazone, Diabetes, vol.46, issue.11, pp.1678-1683, 1997.
DOI : 10.2337/diabetes.46.11.1678

K. Mishima, T. Watabe, A. Saito, Y. Yoshimatsu, and N. Imaizumi, Prox1 Induces Lymphatic Endothelial Differentiation via Integrin ??9 and Other Signaling Cascades, Molecular Biology of the Cell, vol.18, issue.4, pp.1421-1429, 2007.
DOI : 10.1091/mbc.E06-09-0780

A. Mishra and E. Newman, Inhibition of inducible nitric oxide synthase reverses the loss of functional hyperemia in diabetic retinopathy, Glia, vol.6, issue.16, pp.1996-2004, 2010.
DOI : 10.1002/glia.21068

J. Miyazaki, K. Araki, E. Yamato, H. Ikegami, and T. Asano, Establishment of a Pancreatic ?? Cell Line That Retains Glucose-Inducible Insulin Secretion: Special Reference to Expression of Glucose Transporter Isoforms*, Endocrinology, vol.127, issue.1, pp.126-132, 1990.
DOI : 10.1210/endo-127-1-126

L. Moreno, D. Henauw, S. Gonzalez-gross, M. Kersting, M. Molnar et al., Design and implementation of the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study, International Journal of Obesity, vol.32, issue.5, pp.4-11, 2008.
DOI : 10.1016/S0899-9007(03)00040-6

A. Morris, B. Voight, T. Teslovich, T. Ferreira, and A. Segre, Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes, Nature Genetics, vol.224, issue.9, pp.981-990, 2012.
DOI : 10.1038/ng1508

E. Nagy, G. Vicente-rodriguez, Y. Manios, L. Beghin, and C. Iliescu, Harmonization process and reliability assessment of anthropometric measurements in a multicenter study in adolescents, International Journal of Obesity, vol.70, issue.5, pp.58-65, 2008.
DOI : 10.1007/s00592-003-0086-y

P. Newsholme, K. Bender, A. Kiely, and L. Brennan, Amino acid metabolism, insulin secretion and diabetes, Biochemical Society Transactions, vol.35, issue.5, pp.1180-1186, 2007.
DOI : 10.1042/BST0351180

T. Nishikawa, D. Kukidome, K. Sonoda, K. Fujisawa, and T. Matsuhisa, Impact of mitochondrial ROS production on diabetic vascular complications, Diabetes Research and Clinical Practice, vol.77, issue.3, pp.41-45, 2007.
DOI : 10.1016/j.diabres.2007.01.031

C. Nolan, J. Leahy, V. Delghingaro-augusto, J. Moibi, and K. Soni, Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling, Diabetologia, vol.50, issue.Suppl 3, pp.2120-2130, 2006.
DOI : 10.1007/s00125-006-0305-5

L. Nordquist, K. Shimada, T. Ishii, D. Furuya, and A. Kamikawa, Proinsulin C-peptide prevents type-1 diabetes-induced decrease of renal Na+-K+-ATPase ??1-subunit in rats, Diabetes/Metabolism Research and Reviews, vol.47, issue.3, pp.193-199, 2010.
DOI : 10.1002/dmrr.1071

L. Ohlson, B. Larsson, K. Svardsudd, L. Welin, and H. Eriksson, The Influence of Body Fat Distribution on the Incidence of Diabetes Mellitus: 13.5 Years of Follow-up of the Participants in the Study of Men Born in 1913, Diabetes, vol.34, issue.10, pp.1055-1058, 1985.
DOI : 10.2337/diab.34.10.1055

G. Oliver, B. Sosa-pineda, S. Geisendorf, E. Spana, and C. Doe, Prox 1, a prospero-related homeobox gene expressed during mouse development, Mechanisms of Development, vol.44, issue.1, pp.3-16, 1993.
DOI : 10.1016/0925-4773(93)90012-M

M. Pan, T. Chang, H. Chang, J. Su, and H. Wang, Sumoylation of Prox1 controls its ability to induce VEGFR3 expression and lymphatic phenotypes in endothelial cells, Journal of Cell Science, vol.122, issue.18, pp.3358-3364, 2009.
DOI : 10.1242/jcs.050005

S. Park, K. Ds, J. Daily, and S. Kim, Serum prolactin concentrations determine whether they improve or impair ??-cell function and insulin sensitivity in diabetic rats, Diabetes/Metabolism Research and Reviews, vol.34, issue.6, pp.564-574, 2011.
DOI : 10.1002/dmrr.1215

C. Patel, J. Bhattacharya, and A. Butte, An Environment-Wide Association Study (EWAS) on Type 2 Diabetes Mellitus, PLoS ONE, vol.2, issue.5, p.10746, 2010.
DOI : 10.1371/journal.pone.0010746.s010

M. Peterhoff, A. Sieg, M. Brede, C. Chao, and L. Hein, Inhibition of insulin secretion via distinct signaling pathways in alpha2-adrenoceptor knockout mice, European Journal of Endocrinology, vol.149, issue.4, pp.343-350, 2003.
DOI : 10.1530/eje.0.1490343

J. Petrie, E. Pearson, and C. Sutherland, Implications of genome wide association studies for the understanding of type 2 diabetes pathophysiology, Biochemical Pharmacology, vol.81, issue.4, pp.471-477, 2011.
DOI : 10.1016/j.bcp.2010.11.010

T. Petrova, A. Nykanen, C. Norrmen, K. Ivanov, and L. Andersson, Transcription Factor PROX1 Induces Colon Cancer Progression by Promoting the Transition from Benign to Highly Dysplastic Phenotype, Cancer Cell, vol.13, issue.5, pp.407-419, 2008.
DOI : 10.1016/j.ccr.2008.02.020

URL : https://hal.archives-ouvertes.fr/hal-00282904

L. Phillips and J. Prins, Update on incretin hormones, Annals of the New York Academy of Sciences, vol.362, issue.Suppl. 2, pp.55-74, 2011.
DOI : 10.1111/j.1749-6632.2012.06491.x

O. Pinhas-hamiel and P. Zeitler, The global spread of type 2 diabetes mellitus in children and adolescents, The Journal of Pediatrics, vol.146, issue.5
DOI : 10.1016/j.jpeds.2004.12.042

O. Pinhas-hamiel and P. Zeitler, Acute and chronic complications of type 2 diabetes mellitus in children and adolescents, The Lancet, vol.369, issue.9575, pp.1823-1831, 2007.
DOI : 10.1016/S0140-6736(07)60821-6

D. Pipeleers, Heterogeneity in pancreatic beta-cell population, Diabetes, vol.41, issue.7, pp.777-781, 1992.
DOI : 10.2337/diabetes.41.7.777

V. Poitout, D. Hagman, R. Stein, I. Artner, and R. Robertson, Regulation of the insulin gene by glucose and fatty acids, J.Nutr, vol.136, pp.873-876, 2006.

J. Pomerleau, P. Mckeigue, and N. Chaturvedi, Relationships of fasting and postload glucose levels to sex and alcohol consumption Are American Diabetes Association criteria biased against detection of diabetes in women? Diabetes Care, pp.430-433, 1999.

M. Prentki, E. Joly, E. Assaad, W. Roduit, and R. , Malonyl-CoA Signaling, Lipid Partitioning, and Glucolipotoxicity: Role in ??-Cell Adaptation and Failure in the Etiology of Diabetes, Diabetes, vol.51, issue.Supplement 3, pp.405-413, 2002.
DOI : 10.2337/diabetes.51.2007.S405

I. Prokopenko, C. Langenberg, J. Florez, R. Saxena, and N. Soranzo, Variants in MTNR1B influence fasting glucose levels, Nature Genetics, vol.271, issue.1, pp.77-81, 2009.
DOI : 10.1111/j.1600-079X.2007.00426.x

Q. Qiao, T. Nakagami, J. Tuomilehto, K. Borch-johnsen, and B. Balkau, Comparison of the fasting and the 2-h glucose criteria for diabetes in different Asian cohorts, Diabetologia, vol.43, issue.12, pp.1470-1475, 2000.
DOI : 10.1007/s001250051557

J. Qin, D. Gao, Q. Jiang, Q. Zhou, and Y. Kong, Prospero-Related Homeobox (Prox1) Is a Corepressor of Human Liver Receptor Homolog-1 and Suppresses the Transcription of the Cholesterol 7-??-Hydroxylase Gene, Molecular Endocrinology, vol.18, issue.10, pp.2424-2439, 2004.
DOI : 10.1210/me.2004-0009

I. Quesada, E. Tuduri, C. Ripoll, and A. Nadal, Physiology of the pancreatic ??-cell and glucagon secretion: role in glucose homeostasis and diabetes, Journal of Endocrinology, vol.199, issue.1, pp.5-19, 2008.
DOI : 10.1677/JOE-08-0290

R. Rabasa-lhoret and M. Laville, How to measure insulin sensitivity in clinical practice, Diabetes Metab, vol.27, pp.201-208, 2001.

W. Rathmann, B. Kowall, and G. Giani, Type 2 diabetes: unravelling the interaction between genetic predisposition and lifestyle, Diabetologia, vol.26, issue.Suppl 3, pp.2217-2219, 2011.
DOI : 10.1007/s00125-011-2222-5

P. Ravassard, Y. Hazhouz, S. Pechberty, E. Bricout-neveu, and M. Armanet, A genetically engineered human pancreatic ?? cell line exhibiting glucose-inducible insulin secretion, Journal of Clinical Investigation, vol.121, issue.9, pp.3589-3597, 2011.
DOI : 10.1172/JCI58447DS1

A. Rebai, Linkage analysis for complex diseases: a new life for an old method], Arch.Inst.Pasteur Tunis, vol.77, pp.25-35, 2000.

R. Retnakaran, C. Cull, K. Thorne, A. Adler, and R. Holman, Risk Factors for Renal Dysfunction in Type 2 Diabetes: U.K. Prospective Diabetes Study 74, Diabetes, vol.55, issue.6, pp.1832-1839, 2006.
DOI : 10.2337/db05-1620

I. Reynisdottir, G. Thorleifsson, R. Benediktsson, G. Sigurdsson, and V. Emilsson, Localization of a Susceptibility Gene for Type 2 Diabetes to Chromosome 5q34???q35.2, The American Journal of Human Genetics, vol.73, issue.2, pp.323-335, 2003.
DOI : 10.1086/377139

T. Rice, N. Schork, and D. Rao, Methods for Handling Multiple Testing, Adv.Genet, vol.60, pp.293-308, 2008.
DOI : 10.1016/S0065-2660(07)00412-9

M. Ridderstrale and L. Groop, Genetic dissection of type 2 diabetes, Molecular and Cellular Endocrinology, vol.297, issue.1-2, pp.10-17, 2009.
DOI : 10.1016/j.mce.2008.10.002

URL : https://hal.archives-ouvertes.fr/hal-00532093

C. Risebro, R. Searles, A. Melville, E. Ehler, and J. N. , Prox1 maintains muscle structure and growth in the developing heart, Development, vol.136, issue.3, pp.495-505, 2009.
DOI : 10.1242/dev.030007

K. Rothman, S. Greenland, and A. Walker, CONCEPTS OF INTERACTION, American Journal of Epidemiology, vol.112, issue.4, pp.467-470, 1980.
DOI : 10.1093/oxfordjournals.aje.a113015

S. Sasson, Y. Ashhab, D. Melloul, and E. Cerasi, Autoregulation of Glucose Transport: Effects of Glucose on Glucose Transporter Expression and Cellular Location in Muscle, Adv.Exp.Med.Biol, vol.334, pp.113-127, 1993.
DOI : 10.1007/978-1-4615-2910-1_9

R. Saxena, B. Voight, V. Lyssenko, N. Burtt, and P. De-bakker, Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels, Science, vol.316, pp.1331-1336, 2007.

A. Schroeder, O. Mueller, S. Stocker, R. Salowsky, and M. Leiber, The RIN: an RNA integrity number for assigning integrity values to RNA measurements, BMC Molecular Biology, vol.7, issue.1, p.3, 2006.
DOI : 10.1186/1471-2199-7-3

L. Scott, K. Mohlke, L. Bonnycastle, C. Willer, and Y. Li, A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants, Science, vol.316, issue.5829, pp.1341-1345, 2007.
DOI : 10.1126/science.1142382

R. Scott, V. Lagou, R. Welch, E. Wheeler, and M. Montasser, Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways, Nature Genetics, vol.41, issue.9, pp.991-1005, 2012.
DOI : 10.1086/519795

N. Sekine, C. Wollheim, and T. Fujita, GH Signalling in Pancreatic ??-Cells, Endocrine Journal, vol.45, issue.Suppl, pp.33-40, 1998.
DOI : 10.1507/endocrj.45.Suppl_S33

J. Seufert, Leptin effects on pancreatic beta-cell gene expression and function, Diabetes, vol.53, 2004.

J. Shaw, . De-court, E. Boyko, and P. Zimmet, Impact of new diagnostic criteria for diabetes on different populations, Diabetes Care, vol.22, issue.5, pp.762-766, 1999.
DOI : 10.2337/diacare.22.5.762

H. Sies, Role of reactive oxygen species in biological processes, Klinische Wochenschrift, vol.279, issue.21-23, pp.965-968, 1991.
DOI : 10.1007/BF01645140

R. Singh, J. Artaza, W. Taylor, M. Braga, and X. Yuan, Testosterone Inhibits Adipogenic Differentiation in 3T3-L1 Cells: Nuclear Translocation of Androgen Receptor Complex with ??-Catenin and T-Cell Factor 4 May Bypass Canonical Wnt Signaling to Down-Regulate Adipogenic Transcription Factors, Endocrinology, vol.147, issue.1, pp.141-154, 2006.
DOI : 10.1210/en.2004-1649

M. Skelin, M. Rupnik, and A. Cencic, Pancreatic beta cell lines and their applications in diabetes mellitus research, ALTEX, vol.27, pp.105-113, 2010.
DOI : 10.14573/altex.2010.2.105

R. Sladek, G. Rocheleau, J. Rung, C. Dina, and L. Shen, A genome-wide association study identifies novel risk loci for type 2 diabetes, Nature, vol.70, issue.7130, pp.881-885, 2007.
DOI : 10.1038/nature05616

URL : https://hal.archives-ouvertes.fr/hal-00173692

M. Slaughter, T. Lohman, R. Boileau, C. Horswill, and R. Stillman, Skinfold equations for estimation of body fatness in children and youth, Hum.Biol, vol.60, pp.709-723, 1988.

K. Small, A. Hedman, E. Grundberg, A. Nica, and G. Thorleifsson, Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes, Nature Genetics, vol.43, issue.6, pp.561-564, 2011.
DOI : 10.1371/journal.pgen.1000529

G. Smyth and T. Speed, Normalization of cDNA microarray data, Methods, vol.31, issue.4, pp.265-273, 2003.
DOI : 10.1016/S1046-2023(03)00155-5

K. Song, T. Li, and J. Chiang, A Prospero-related Homeodomain Protein Is a Novel Co-regulator of Hepatocyte Nuclear Factor 4?? That Regulates the Cholesterol 7??-Hydroxylase Gene, Journal of Biological Chemistry, vol.281, issue.15, pp.10081-10088, 2006.
DOI : 10.1074/jbc.M513420200

B. Sosa-pineda, J. Wigle, and G. Oliver, Hepatocyte migration during liver development requires Prox1

Y. Stefan, L. Orci, F. Malaisse-lagae, A. Perrelet, and Y. Patel, Quantitation of Endocrine Cell Content in the Pancreas of Nondiabetic and Diabetic Humans, Diabetes, vol.31, issue.8, pp.694-700, 1982.
DOI : 10.2337/diab.31.8.694

K. Steffensen, E. Holter, A. Bavner, M. Nilsson, and M. Pelto-huikko, Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ-F1 homologue, EMBO reports, vol.16, issue.6, pp.613-619, 2004.
DOI : 10.1038/385552a0

D. Stein, V. Esser, B. Stevenson, K. Lane, and J. Whiteside, Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat., Journal of Clinical Investigation, vol.97, issue.12, pp.2728-2735, 1996.
DOI : 10.1172/JCI118727

D. Stein, B. Stevenson, M. Chester, M. Basit, and M. Daniels, The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation., Journal of Clinical Investigation, vol.100, issue.2, pp.398-403, 1997.
DOI : 10.1172/JCI119546

D. Stoffers, N. Zinkin, V. Stanojevic, W. Clarke, and J. Habener, Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence, Nature Genetics, vol.6, issue.1, pp.106-110, 1997.
DOI : 10.1210/me.9.9.1127

J. Storey and R. Tibshirani, Statistical significance for genomewide studies, Proceedings of the National Academy of Sciences, vol.100, issue.16, pp.9440-9445, 2003.
DOI : 10.1073/pnas.1530509100

M. Strowski, R. Parmar, A. Blake, and J. Schaeffer, Somatostatin Inhibits Insulin and Glucagon Secretion via Two Receptor Subtypes: An in Vitro Study of Pancreatic Islets from Somatostatin Receptor 2 Knockout Mice, Endocrinology, vol.141, issue.1, pp.111-117, 2000.
DOI : 10.1210/en.141.1.111

H. Su and S. Li, Molecular features of human ubiquitin-like SUMO genes and their encoded proteins, Gene, vol.296, issue.1-2
DOI : 10.1016/S0378-1119(02)00843-0

A. Tabak, M. Jokela, T. Akbaraly, E. Brunner, and M. Kivimaki, Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study, The Lancet, vol.373, issue.9682, pp.2215-2221, 2009.
DOI : 10.1016/S0140-6736(09)60619-X

M. Takahashi, T. Yoshimoto, M. Shimoda, T. Kono, and M. Koizumi, Loss of Function of the Candidate Tumor Suppressor prox1 by RNA Mutation in Human Cancer Cells, Neoplasia, vol.8, issue.12, pp.1003-1010, 2006.
DOI : 10.1593/neo.06595

M. Teran-garcia and C. Bouchard, Genetics of the metabolic syndrome, Applied Physiology, Nutrition, and Metabolism, vol.32, issue.1, pp.89-114, 2007.
DOI : 10.1139/h06-102

B. Thorens, Brain glucose sensing and neural regulation of insulin and glucagon secretion, Diabetes, Obesity and Metabolism, vol.32, issue.Suppl 6, pp.82-88, 2011.
DOI : 10.1111/j.1463-1326.2011.01453.x

D. Tregouet, S. Escolano, L. Tiret, A. Mallet, and J. Golmard, A new algorithm for haplotype-based association analysis: the Stochastic-EM algorithm, Annals of Human Genetics, vol.85, issue.2, pp.165-177, 2004.
DOI : 10.1159/000048602

P. Vague and L. Nguyen, Rationale and Methods for the Estimation of Insulin Secretion in a Given Patient: From Research to Clinical Practice, Diabetes, vol.51, issue.Supplement 1, pp.240-244, 2002.
DOI : 10.2337/diabetes.51.2007.S240

J. Venter, M. Adams, E. Myers, P. Li, and R. Mural, The Sequence of the Human Genome, Science, vol.291, issue.5507, pp.1304-1351, 2001.
DOI : 10.1126/science.1058040

URL : https://hal.archives-ouvertes.fr/hal-00465088

B. Versmold, J. Felsberg, T. Mikeska, D. Ehrentraut, and J. Kohler, Epigenetic silencing of the candidate tumor suppressor gene PROX1 in sporadic breast cancer, International Journal of Cancer, vol.59, issue.3, pp.547-554, 2007.
DOI : 10.1002/ijc.22705

B. Voight, L. Scott, V. Steinthorsdottir, A. Morris, and C. Dina, Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis, Nature Genetics, vol.37, issue.7, pp.579-589, 2010.
DOI : 10.1038/ng.609

J. Wahren, K. Ekberg, J. Johansson, M. Henriksson, and A. Pramanik, Role of C-peptide in human physiology, Am.J.Physiol Endocrinol.Metab, vol.278, pp.759-768, 2000.

J. Wang, G. Kilic, M. Aydin, Z. Burke, and G. Oliver, Prox1 activity controls pancreas morphogenesis and participates in the production of ???secondary transition??? pancreatic endocrine cells, Developmental Biology, vol.286, issue.1, pp.182-194, 2005.
DOI : 10.1016/j.ydbio.2005.07.021

L. Wang, J. Zhu, S. Shan, Y. Qin, and Y. Kong, Repression of interferon-?? expression in T cells by Prospero-related Homeobox protein, Cell Research, vol.172, issue.9, pp.911-920, 2008.
DOI : 10.1093/nar/gki979

W. Wang, B. Barratt, D. Clayton, and J. Todd, Genome-wide association studies: theoretical and practical concerns, Nature Reviews Genetics, vol.60, issue.2, pp.109-118, 2005.
DOI : 10.1093/jnci/djh075

J. Wardle, S. Carnell, C. Haworth, and R. Plomin, Evidence for a strong genetic influence on childhood adiposity despite the force of the obesogenic environment, Am.J.Clin.Nutr, vol.87, pp.398-404, 2008.

F. Wei, K. Nagashima, T. Ohshima, Y. Saheki, and Y. Lu, Cdk5-dependent regulation of glucose-stimulated insulin secretion, Nature Medicine, vol.48, issue.10, pp.1104-1108, 2005.
DOI : 10.1083/jcb.200308110

P. Westermark, A. Andersson, and G. Westermark, Islet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus, Physiological Reviews, vol.91, issue.3, pp.795-826, 2011.
DOI : 10.1152/physrev.00042.2009

J. Westmoreland, G. Kilic, C. Sartain, S. Sirma, and J. Blain, Pancreas-Specific Deletion of Prox1 Affects Development and Disrupts Homeostasis of the Exocrine Pancreas, Gastroenterology, vol.142, issue.4, pp.999-1009, 2012.
DOI : 10.1053/j.gastro.2011.12.007

J. Wigle, N. Harvey, M. Detmar, I. Lagutina, and G. Grosveld, An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype, The EMBO Journal, vol.21, issue.7, pp.1505-1513, 2002.
DOI : 10.1093/emboj/21.7.1505

J. Wigle and G. Oliver, Prox1 Function Is Required for the Development of the Murine Lymphatic System, Cell, vol.98, issue.6, pp.769-778, 1999.
DOI : 10.1016/S0092-8674(00)81511-1

S. Yamagishi and T. Imaizumi, Diabetic Vascular Complications: Pathophysiology, Biochemical Basis and Potential Therapeutic Strategy, Current Pharmaceutical Design, vol.11, issue.18, pp.2279-2299, 2005.
DOI : 10.2174/1381612054367300

S. Yamagishi and T. Imaizumi, Molecular mechanism of diabetic retinopathy: role of advanced glycation end products(AGEs) and their receptor (RAGE) in the pathogenesis of diabetic retinopathy, Nihon Ganka Gakkai Zasshi, vol.109, pp.338-345, 2005.

S. Yamagishi, K. Nakamura, T. Matsui, S. Ueda, and K. Fukami, Agents that block advanced glycation end product (AGE)-RAGE (receptor for AGEs)-oxidative stress system: a novel therapeutic strategy for diabetic vascular complications, Expert Opinion on Investigational Drugs, vol.27, issue.7, pp.983-996, 2008.
DOI : 10.1016/S0140-6736(98)07019-6

E. Zeggini, M. Weedon, C. Lindgren, T. Frayling, and K. Elliott, Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes, Science, vol.316, issue.5829, pp.1336-1341, 2007.
DOI : 10.1126/science.1142364

H. Zhao, T. Yang, B. Madakashira, C. Thiels, and C. Bechtle, Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation, Developmental Biology, vol.318, issue.2, pp.276-288, 2008.
DOI : 10.1016/j.ydbio.2008.03.028