D. Accili, S. C. Talchai, J. Y. Kim-muller, F. Cinti, E. Ishida et al., , 2016.

. Metab, , vol.18, pp.117-122

R. L. Batterham, H. Heffron, S. Kapoor, J. E. Chivers, K. Chandarana et al., Critical role for peptide YY in protein-mediated satiation and body-weight regulation, Cell Metab, vol.4, pp.223-233, 2006.

A. Beenken and M. Mohammadi, The FGF family: biology, pathophysiology and therapy, Nat Rev Drug Discov, vol.8, pp.235-253, 2009.

V. Chandra, O. Albagli-curiel, B. Hastoy, J. Piccand, C. Randriamampita et al., , vol.9, pp.2206-2218, 2014.

F. Cinti, R. Bouchi, J. Y. Kim-muller, Y. Ohmura, P. R. Sandoval et al., Evidence of ?-cell dedifferentiation in human type 2 diabetes, J Clin Endocrinol Metab, vol.101, pp.1044-1054, 2016.

T. Dahan, O. Ziv, E. Horwitz, H. Zemmour, J. Lavi et al., Pancreatic ?-Cells express the fetal islet hormone gastrin in rodent and human diabetes, Diabetes, vol.66, pp.426-436, 2017.

V. Dominguez, C. Raimondi, S. Somanath, M. Bugliani, M. K. Loder et al.,

N. Divecha, G. Silva-xavier, . Da, L. Marselli, and S. J. Persaud, , 2011.

B. Duvillié, M. Attali, V. Aiello, E. Quemeneur, and R. Scharfmann, Labelretaining cells in the rat pancreas: Location and differentiation potential in vitro, Diabetes, vol.52, pp.2035-2042, 2003.

B. N. Ediger, H. W. Lim, C. Juliana, D. N. Groff, L. Q. Williams et al., , vol.127, pp.215-229, 2017.

E. Ferrannini, The stunned ? cell: A brief history, Cell Metab, vol.11, pp.349-352, 2010.

G. Finak, A. Mcdavid, M. Yajima, J. Deng, V. Gersuk et al., , 2015.

Y. Hang, T. Yamamoto, R. K. Benninger, M. Brissova, M. Guo et al., The MafA transcription factor becomes essential to islet b-cells soon after birth, Diabetes, vol.63, 1994.

A. W. Hart, N. Baeza, A. Apelqvist, and H. Edlund, Attenuation of FGF signalling in mouse beta-cells leads to diabetes, Nature, vol.408, pp.864-868, 2000.

E. Hubbell, W. Liu, M. , and R. , , 2002.

, Bioinformatics, vol.18, pp.1585-1592

E. Ishida, J. Y. Kim-muller, A. , and D. , Pair-Feeding, but not Insulin, 2017.

J. C. Jonas, A. Sharma, W. Hasenkamp, H. Ilkova, G. Patanè et al., , 1999.

, J Biol Chem, vol.274, pp.14112-14121

J. W. Jonker, J. M. Suh, A. R. Atkins, M. Ahmadian, P. Li et al., A PPAR?-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis, Nature, vol.485, pp.391-394, 2012.

A. Kauffmann, R. Gentleman, and W. Huber, , 2009.

Y. Kawaguchi, Sox9 and programming of liver and pancreatic progenitors, J Clin Invest, vol.123, pp.1881-1886, 2013.

A. E. Kearns, S. Khosla, and P. J. Kostenuik, , 2008.

D. Kim, B. Langmead, and S. L. Salzberg, HISAT: a fast spliced aligner with low memory requirements, Nat Methods, vol.12, pp.357-360, 2015.

N. G. Kondegowda, R. Fenutria, I. R. Pollack, M. Orthofer, A. Garcia-ocaña et al., Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-?B Ligand Pathway, 2015.

, Cell Metab, vol.22, pp.77-85

L. I. Larsson, J. F. Rehfeld, F. Sundler, and R. Hakanson, Pancreatic gastrin in foetal and neonatal rats, Nature, vol.262, pp.609-610, 1976.

Y. Liao, G. K. Smyth, and W. Shi, FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features, Bioinformatics, vol.30, pp.923-930, 2014.

M. I. Love, W. Huber, A. , and S. , , 2014.

L. Marselli, M. Suleiman, M. Masini, D. Campani, M. Bugliani et al., Are we overestimating the loss of beta cells in type 2 diabetes?, Diabetologia, vol.57, pp.362-365, 2014.

W. Nishimura, S. Takahashi, Y. , and K. , , 2014.

T. S. Olsen, Lipomatosis of the pancreas in autopsy material and its relation to age and overweight, Acta Pathol. Microbiol. Scand. Ser. A, vol.86, pp.367-373, 1978.

D. M. Ornitz, J. Xu, J. S. Colvin, D. G. Mcewen, C. A. Macarthur et al., Receptor specificity of the fibroblast growth factor family, J Biol Chem, vol.271, pp.15292-15297, 1996.

R. Patro, G. Duggal, and C. Kingsford, Salmon: Accurate, Versatile and Ultrafast Quantification from RNA-seq Data using Lightweight-Alignment, vol.21592, 2015.

M. Prentki, F. F. Matschinsky, and S. R. Madiraju, Metabolic signaling in fuelinduced insulin secretion, Cell Metab, vol.18, pp.162-185, 2013.

S. Puri, H. Akiyama, and M. Hebrok, , 2013.

, Genes Dev, vol.27, pp.2563-2575

P. Ravassard, Y. Hazhouz, S. Pechberty, E. Bricout-neveu, M. Armanet et al., , 2011.

S. Rieck, P. White, J. Schug, A. J. Fox, O. Smirnova et al., The transcriptional response of the islet to pregnancy in mice, Mol. Endocrinol, vol.23, pp.1702-1712, 2009.

M. E. Ritchie, B. Phipson, D. Wu, Y. Hu, C. W. Law et al., , 2015.

R. Scharfmann, M. Didiesheim, P. Richards, V. Chandra, M. Oshima et al.,

, Mass production of functional human pancreatic ?-cells: why and how? Diabetes, Obes. Metab, vol.18, pp.128-136

J. Schrader, W. Rennekamp, U. Niebergall, M. Schoppet, H. Jahr et al., , vol.50, pp.1243-1247, 2007.

A. Segerstolpe, A. Palasantza, P. Eliasson, E. Andersson, A. Andreasson et al., Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes, Cell Metab, vol.24, pp.593-607, 2016.

C. Sheng, F. Li, Z. Lin, M. Zhang, P. Yang et al., , 2016.

, Reversibility of ?-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse, J. Diabetes Res, vol.2016, pp.1-11

K. G. Slepchenko, N. A. Daniels, A. Guo, and Y. Li, Autocrine effect of Zn2+ on the glucose-stimulated insulin secretion, Endocrine, vol.50, pp.110-122, 2015.

A. Swisa, D. Avrahami, N. Eden, J. Zhang, E. Feleke et al., , vol.127, pp.230-243, 2017.

C. Talchai, S. Xuan, H. V. Lin, L. Sussel, A. et al., , pp.1223-1234, 2012150.

B. L. Wajchenberg, ?-cell failure in diabetes and preservation by clinical treatment, 2007.

, Endocr Rev, vol.28, pp.187-218

S. Wang, Q. Yang, S. Yu, R. Pan, D. Jiang et al., , 2016.

Z. Wang, N. W. York, C. G. Nichols, and M. S. Remedi, , 2014.

G. C. Weir and S. Bonner-weir, , 2011.

G. C. Weir, C. Aguayo-mazzucato, and S. Bonner-weir, ?-Cell Dedifferentiation in Diabetes Is Important, But What Is It? Islets, vol.5, pp.233-237, 2013.

M. G. White, J. A. Shaw, T. , and R. , Type 2 Diabetes: The Pathologic Basis of Reversible ?-Cell Dysfunction, Diabetes Care, vol.39, pp.2080-2088, 2016.

R. Xie, L. J. Everett, H. W. Lim, N. A. Patel, J. Schug et al.,

K. A. D'amour and A. J. Robins, , 2013.

J. Ye, G. Coulouris, I. Zaretskaya, I. Cutcutache, S. Rozen et al., , 2012.

, Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction, BMC Bioinformatics, vol.13, p.134

D. Accili, S. C. Talchai, J. Y. Kim-muller, F. Cinti, E. Ishida et al., When -cells fail: lessons from dedifferentiation, Diabetes, Obes. Metab, vol.18, pp.117-118
DOI : 10.1111/dom.12723

URL : https://onlinelibrary.wiley.com/doi/pdf/10.1111/dom.12723

C. Aguayo-mazzucato and S. Bonner-weir, Pancreatic Cell Regeneration as a Possible Therapy for Diabetes, Cell Metab
DOI : 10.1016/j.cmet.2017.08.007

URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762410

I. Artner, J. Le-lay, Y. Hang, L. Elghazi, J. C. Schisler et al., MafB: an activator of the glucagon gene expressed in developing islet alphaand beta-cells, Diabetes, vol.55, pp.97-101

S. Assady, G. Maor, M. Amit, J. Itskovitz-eldor, K. L. Skorecki et al.,

, Insulin Production by Human Embryonic Stem Cells, Diabetes, vol.50, pp.1691-1697

H. Beck-nielsen and L. C. Groop, Metabolic and genetic characterization of prediabetic states. Sequence of events leading to non-insulin-dependent diabetes mellitus, J Clin Invest, vol.94, pp.1714-1731, 1994.
DOI : 10.1172/jci117518

URL : http://www.jci.org/articles/view/117518/files/pdf

J. R. Benthuysen, A. C. Carrano, and M. Sander, Advances in cell replacement and regeneration strategies for treating diabetes, J Clin Invest, vol.126, pp.651-660
DOI : 10.1172/jci87439

URL : http://www.jci.org/articles/view/87439/files/pdf

H. M. Blau and D. Baltimore, Differentiation requires continuous regulation, J Cell Biol, vol.112, pp.781-78, 1991.
DOI : 10.1083/jcb.112.5.781

URL : http://jcb.rupress.org/content/112/5/781.full.pdf

S. Bonner-weir, P. A. In't-veld, and G. C. Weir, Reanalysis of study of pancreatic effects of incretin therapy: methodological deficiencies, Diabetes Obes Metab

D. E. Borst and D. S. Mcdevitt, Eye lens regeneration and the crystallins in the adult newt, Notophthalmus viridescens, Exp Eye Res, vol.45, pp.419-441, 1987.

V. Brezar, J. C. Carel, C. Boitard, and R. Mallone, Beyond the hormone: Insulin as an autoimmune target in type 1 diabetes, Endocr Rev, vol.32, pp.6-669

M. Brissova, M. J. Fowler, W. E. Nicholson, A. Chu, B. Hirshberg et al., Assessment of Human Pancreatic Islet Architecture and Composition by Laser Scanning Confocal Microscopy, J. Histochem. Cytochem, vol.53, pp.1087-1097
DOI : 10.1369/jhc.5c6684.2005

URL : https://journals.sagepub.com/doi/pdf/10.1369/jhc.5C6684.2005

J. P. Brockes, Amphibian Limb Regeneration: Rebuilding a Complex Structure, Science (80-), vol.276, pp.81-87, 1997.
DOI : 10.1126/science.276.5309.81

A. E. Butler, J. Janson, S. Bonner-weir, R. Ritzel, R. A. Rizza et al., ?-Cell Deficit and Increased ?-Cell Apoptosis in Humans With Type ? Diabetes, Diabetes, vol.52, pp.10-110
DOI : 10.2337/diabetes.52.1.102

URL : http://diabetes.diabetesjournals.org/content/52/1/102.full.pdf

A. E. Butler, L. Cao-minh, R. Galasso, R. A. Rizza, A. Corradin et al.,

, Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy, Diabetologia, vol.53, pp.167-176

A. E. Butler, M. Campbell-thompson, T. Gurlo, D. W. Dawson, M. Atkinson et al., , p.1

A. E. Butler, S. Dhawan, J. Hoang, M. Cory, K. Zeng et al., ?016). -Cell deficit in obese type ? diabetes, a minor role of -Cell dedifferentiation and degranulation, J Clin Endocrinol Metab, vol.101, pp.5-5

M. Campbell-thompson, C. Wasserfall, J. Kaddis, -. Albanese, A. Neill et al., Network for Pancreatic Organ Donors with Diabetes (nPOD): developing a tissue biobank for type 1 diabetes, Diabetes Metab Res Rev, vol.28, pp.608-617
DOI : 10.1002/dmrr.2316

URL : http://europepmc.org/articles/pmc3456997?pdf=render

R. A. Cantrell, C. I. Alatorre, E. J. Davis, V. Zarotsky, E. Le-nestour et al., A review of treatment response in type ? diabetes: Assessing the role of patient heterogeneity, Diabetes, Obes. Metab, vol.12, pp.845-857

S. Carpenter, M. Rigaud, M. Barile, T. J. Priest, L. Perez et al., An Interlinear Transliteration and English Translation of Portions of The Ebers Papyrus Possibly Having to Do With Diabetes Mellitus, 1998.

F. Cinti, R. Bouchi, J. Y. Kim-muller, Y. Ohmura, P. R. Sandoval et al., Evidence of -cell dedifferentiation in human type ? diabetes, J Clin Endocrinol Metab, vol.101, issue.?016, pp.1044-1054

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

A. Clark, L. C. Jones, E. De-koning, B. C. Hansen, and D. R. Matthews, Decreased insulin secretion in type ? diabetes: A problem of cellular mass or function?, Diabetes, vol.50, pp.169-71

G. W. Cline, K. F. Petersen, M. Krssak, J. Shen, R. S. Hundal et al., , 1999.

M. Cnop, S. J. Hughes, M. Igoillo-esteve, M. B. Hoppa, F. Sayyed et al.,

K. T. Coppieters, V. Herrath, and M. G. , Histopathology of type 1 diabetes: Old paradigms and new insights, Rev. Diabet. Stud, vol.6, pp.85-96

A. K. Davis, S. N. Dubose, M. J. Haller, K. M. Miller, L. A. Dimeglio et al.,

R. A. Defronzo, The triumvirate: b-cell, muscle, or liver-a collusion responsible for NIDDM, Diabetes, vol.37, pp.667-687, 1988.

R. A. Defronzo and A. M. Goodman, , 1995.

R. A. Defronzo, E. Ferrannini, and D. C. Simonson, Fasting hyperglycemia in noninsulin-dependent diabetes mellitus: Contributions of excessive hepatic glucose production and impaired tissue glucose uptake, Metabolism, vol.38, pp.87-95, 1989.

S. Dhawan, S. Georgia, S. Tschen, G. Fan, and A. Bhushan, Pancreatic Cell Identity Is Maintained by DNA Methylation-Mediated Repression of Arx, Dev Cell, vol.20, pp.419-423

V. Dominguez, C. Raimondi, S. Somanath, M. Bugliani, M. K. Loder et al.,

C. Dorrell, J. Schug, C. F. Lin, P. S. Canaday, A. J. Fox et al., Transcriptomes of the major human pancreatic cell types, Diabetologia, vol.54, issue.?011, pp.8-844

C. Dorrell, J. Schug, P. S. Canaday, H. A. Russ, B. D. Tarlow et al., Human islets contain four distinct subtypes of cells, Nat Commun, vol.7, issue.?016, p.11756

C. Druet, C. Roudier, I. Romon, F. Assogba, I. Bourdel-marchasson et al., Échantillon national témoin représentatif des personnes diabétiques, Entred ?007-?010

S. Efendic, V. Grill, R. Luft, and A. Wajngot, Low insulin response: a marker of prediabetes, Adv Exp Med Biol, vol.246, pp.167-174, 1988.

D. L. Eizirik, S. Sandler, N. Welsh, M. Cetkovic-cvrlje, A. Nieman et al., , vol.93, pp.1968-1974, 1994.

L. Elghazi, A. J. Weiss, D. J. Barker, J. Callaghan, L. Staloch et al., Regulation of Pancreas Plasticity and Malignant Transformation by Akt Signaling, Gastroenterology, vol.136, pp.1091-110

J. Eng, W. A. Kleinman, L. Singh, G. Singh, and J. P. Raufman, Isolation and characterization of exendin-4, an exendin-? analogue, from Heloderma suspectum venom: Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas, J Biol Chem, vol.267, pp.740-7405

, Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, Diabetes Care, vol.20, pp.118-1197, 1997.

M. Franco, U. Bilal, P. Ordunez, M. Benet, A. Morejon et al., Population-wide weight loss and regain in relation to diabetes burden and cardiovascular mortality in Cuba 1980-?010: repeated cross sectional surveys and ecological comparison of secular trends, Br Med J, vol.346, pp.1515-1515

M. Gannon, E. Tweedie-ables, L. Crawford, D. Lowe, M. F. Offield et al.,

A. F. Gazdar, W. L. Chick, H. K. Oie, H. L. Sims, D. L. King et al.,

, Continuous, clonal, insulin-and somatostatin-secreting cell lines established from a transplantable rat islet cell tumor, Proc Natl Acad Sci U S A, vol.77, pp.519-524

W. Gepts, Pathologic anatomy of the pancreas in juvenile diabetes mellitus, Diabetes, vol.14, pp.619-625, 1965.

J. E. Gerich, The genetic basis of type ? diabetes mellitus: Impaired insulin secretion versus impaired insulin sensitivity, Endocr Rev, vol.19, pp.491-50, 1998.

G. K. Gittes, Developmental biology of the pancreas: A comprehensive review, Dev Biol, vol.326, pp.4-5

G. Gradwohl, A. Dierich, M. Lemeur, and F. Guillemot, Neurogenin? Is Required for the Development of the Four Endocrine Cell Lineages of the Pancreas, Proc Natl Acad Sci U S A, vol.97, pp.1607-1611

L. C. Groop, R. C. Bonadonna, S. Delprato, K. Ratheiser, K. Zyck et al., Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance, J Clin Invest, vol.84, pp.5-6, 1989.

G. Gu, J. Dubauskaite, and D. A. Melton, Direct evidence for the pancreatic lineage: NGN?+ cells are islet progenitors and are distinct from duct progenitors, Development, vol.129, pp.447-457

F. Guelfucci, E. Clay, S. Aballéa, R. Lassalle, N. Moore et al.,

Y. Guiot, C. Sempoux, P. Moulin, and J. Rahier,

Y. Hang, T. Yamamoto, R. K. Benninger, M. Brissova, M. Guo et al., The MafA transcription factor becomes essential to islet b-cells soon after birth, Diabetes, vol.63, pp.1994-1999
DOI : 10.2337/db13-1001

URL : http://diabetes.diabetesjournals.org/content/63/6/1994.full.pdf

E. Harja, J. Lord, and J. S. Skyler, An analysis of characteristics of subjects examined for incretin effects on pancreatic pathology, Diabetes Technol Ther, vol.15, pp.609-618

A. W. Hart, N. Baeza, A. Apelqvist, and H. Edlund, Attenuation of FGF signalling in mouse beta-cells leads to diabetes, Nature, vol.408, pp.864-868

C. Hartwich, Die neuen Arzneidrogen aus dem Pflanzenreiche, 1897.
DOI : 10.1007/978-3-662-00287-2

M. F. Hogan and R. L. Hull, The islet endothelial cell: a novel contributor to beta cell secretory dysfunction in diabetes, Diabetologia, vol.60, pp.95-959

R. A. Jackson, M. I. Hawa, J. V. Jaspan, B. M. Sim, L. Disilvio et al.,

M. Janbon, J. Chaptal, A. Vedel, and J. Schaap, Accidents hypoglycémiques graves par un sulfamidothiodiazol (le VK 57 ou ??54 RP), Montpellier Med, vol.441, p.1

R. J. Jarrett, H. Keen, J. H. Fuller, and M. Mccartney, Worsening to diabetes in men with impaired glucose tolerance ("borderline diabetes"), Diabetologia, vol.16, pp.5-5, 1979.

K. A. Johansson, U. Dursun, N. Jordan, G. Gu, F. Beermann et al., Temporal Control of Neurogenin? Activity in Pancreas Progenitors Reveals Competence Windows for the Generation of Different Endocrine Cell Types, Dev Cell, vol.12, pp.457-465

J. C. Jonas, A. Sharma, W. Hasenkamp, H. Ilkova, G. Patanè et al., Chronic hyperglycemia triggers loss of pancreatic cell differentiation in an animal model of diabetes, J Biol Chem, vol.274, pp.1411-141, 1999.

J. W. Jonker, J. M. Suh, A. R. Atkins, M. Ahmadian, P. Li et al., A PPARR-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis, Nature, vol.485, pp.91-94

J. Jonsson, L. Carlsson, T. Edlund, and H. Edlund, Insulin-promoter-factor 1 is required for pancreas development in mice, Nature, vol.371, pp.606-609, 1994.

M. Jumabay, R. Abdmaulen, A. Ly, M. Cubberly, and L. Shahmirian, Pluripotent Stem Cells Derived From Mouse and Human White Mature Adipocytes, Stem Cells Transl. Med, vol.3, pp.161-171

T. Kadowaki, Y. Miyake, R. Hagura, Y. Akanuma, H. Kajinuma et al., , 1984.

C. R. Kahn, Banting lecture: Insulin action, diabetogenes, and the cause of type II diabetes, Diabetes, vol.43, pp.1066-1084, 1994.

S. E. Kahn, M. E. Cooper, D. Prato, and S. , Pathophysiology and treatment of type ? diabetes: Perspectives on the past, present, and future, Lancet, vol.383, pp.1068-108

A. E. Kearns, S. Khosla, and P. J. Kostenuik, Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease, Endocr Rev, vol.29, pp.155-174

H. A. Keenan, J. K. Sun, J. Levine, A. Doria, L. P. Aiello et al., Residual insulin production and pancreatic -cell turnover after 50 years of diabetes: Joslin medalist study, Diabetes, vol.59, pp.846-85

S. P. Kim, M. Ellmerer, G. W. Van-citters, and R. N. Bergman, , p.0

H. King, R. E. Aubert, and W. H. Herman, Global Burden of Diabetes, pp.1995-1995, 1998.

. Prevalence, Estimates and Projections, Diabetes Care, vol.21, pp.1414-1428

G. Kloppel, M. Lohr, K. Habich, M. Oberholzer, P. U. Heitz et al., Islet pathology and the pathogenesis of type 1 and type ? diabetes mellitus revisited, Surv Synth Pathol Res, vol.4, pp.110-111, 1985.

N. G. Kondegowda, R. Fenutria, I. R. Pollack, M. Orthofer, A. Garcia-ocaña et al., Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-?B Ligand Pathway, Cell Metab, vol.22, pp.77-85

K. Kosaka, T. Kuzuya, Y. Akanuma, and R. Hagura, , 1980.

D. A. Lang, D. R. Matthews, M. Burnett, and R. C. Turner, Brief, irregular oscillations of basal plasma insulin and glucose concentrations in diabetic man, Diabetes, vol.30, pp.4-5, 1981.

M. Li, P. Page-mccaw, C. , and W. , FGF1 mediates overnutrition-induced compensatory -cell differentiation, Diabetes, vol.65, pp.96-109

M. Loubatières-mariani, La découverte des sulfamides hypoglycémiants, J Soc Biol, vol.201, pp.1-1

M. Lundberg, L. Krogvold, E. Kuric, K. Dahl-jørgensen, and O. Skog, Expression of interferon-stimulated genes in insulitic pancreatic islets of patients recently diagnosed with type 1 diabetes, Diabetes, vol.65, pp.104-110

A. K. Madiraju, D. M. Erion, Y. Rahimi, X. Zhang, D. T. Braddock et al.,

P. Marcato, C. A. Dean, C. A. Giacomantonio, and L. ,

L. Marselli, J. Thorne, S. Dahiya, D. C. Sgroi, A. Sharma et al.,

L. Marselli, M. Suleiman, M. Masini, D. Campani, M. Bugliani et al., Are we overestimating the loss of beta cells in type ? diabetes, Diabetologia, vol.57, pp.6-65

J. T. Mccluskey, M. Hamid, H. Guo-parke, N. H. Mcclenaghan, R. Gomis et al.,

, Development and functional characterization of insulin-releasing human pancreatic beta cell lines produced by electrofusion, J Biol Chem, vol.286, pp.198-199

L. J. Mccreight, C. J. Bailey, and E. R. Pearson, Metformin and the gastrointestinal tract, Diabetologia, vol.59, pp.4-6

D. S. Mcdevitt, Transdifferentiation in Animals A Model for Differentiation Control, Genomic Adaptability in Somatic Cell Specialization, pp.149-166, 1989.

C. J. Mcgann, S. J. Odelberg, and M. T. Keating, Mammalian myotube dedifferentiation induced by newt regeneration extract, Proc Natl Acad Sci U S A, vol.98, pp.1-699

T. Mezza, G. Muscogiuri, G. P. Sorice, G. Clemente, J. Hu et al., Insulin Resistance Alters Islet Morphology in Nondiabetic Humans, Diabetes, vol.63, pp.994-1007

A. Mitrakou, D. Kelley, M. Mokan, T. Veneman, T. Pangburn et al.,

, Engl J Med, vol.326, p.9

A. S. Moin, S. Dhawan, C. Shieh, P. C. Butler, M. Cory et al.,

A. S. Moin, M. Cory, A. Ong, J. Choi, S. Dhawan et al.,

, Pancreatic Nonhormone Expressing Endocrine Cells in Children With Type 1 Diabetes, J. Endocr. Soc, vol.1, pp.85-95

M. Namenwirth, The inheritance of cell differentiation during limb regeneration in the axolotl, Dev Biol, vol.41, pp.4-56, 1974.

M. Narushima, N. Kobayashi, T. Okitsu, Y. Tanaka, S. A. Li et al., A human beta-cell line for transplantation therapy to control type 1 diabetes, Nat Biotechnol, vol.23, pp.1-74

A. C. Nica, H. Ongen, J. C. Irminger, D. Bosco, T. Berney et al., Cell-type, allelic, and genetic signatures in the human pancreatic beta cell transcriptome, Genome Res, vol.23, pp.1554-156

W. Nishimura, S. Takahashi, Y. , and K. , MafA is critical for maintenance of the mature beta cell phenotype in mice, Diabetologia, vol.58, pp.566-574

S. O'rahilly, R. C. Turner, and D. R. Matthews, Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes, N Engl J Med, vol.318, pp.1-5, 1988.

M. F. Offield, T. L. Jetton, P. A. Labosky, M. Ray, R. W. Stein et al., PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum, Development, vol.122, pp.98-995, 1996.

F. C. Pan, W. , and C. , Pancreas organogenesis: From bud to plexus to gland, Dev. Dyn, vol.240, pp.5-5
DOI : 10.1002/dvdy.22584

G. Parnaud, D. Bosco, T. Berney, F. Pattou, J. Kerr-conte et al., Proliferation of sorted human and rat beta cells, Diabetologia, vol.51, pp.91-100
DOI : 10.1007/s00125-007-0855-1

URL : http://doc.rero.ch/record/311637/files/125_2007_Article_855.pdf

S. Y. Perl, J. A. Kushner, B. A. Buchholz, A. K. Meeker, G. M. Stein et al., Significant human -cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating, J Clin Endocrinol Metab, vol.95, pp.4-9

A. Pisania, G. C. Weir, J. J. O'neil, A. Omer, V. Tchipashvili et al., Quantitative analysis of cell composition and purity of human pancreatic islet preparations, Lab Invest, vol.90, pp.1661-1675

M. Prentki and C. J. Nolan, Islet beta cell failure in type ? diabetes, J Clin Invest, vol.116, pp.180-181
DOI : 10.1172/jci29103

URL : http://www.jci.org/articles/view/29103/files/pdf

S. Puri and M. Hebrok, Cellular plasticity within the pancreas--lessons learned from development, Dev Cell, vol.18, pp.4-56
DOI : 10.1016/j.devcel.2010.02.005

URL : https://doi.org/10.1016/j.devcel.2010.02.005

S. Puri and M. Hebrok, Diabetic Cells: To Be or Not To Be?, Cell, vol.150, pp.110-1104

S. Puri, H. Akiyama, and M. Hebrok, VHL-mediated disruption of Sox9 activity compromises -cell identity and results in diabetes mellitus, Genes Dev, vol.27, pp.56-575

N. Quiskamp, J. E. Bruin, and T. J. Kieffer, Differentiation of human pluripotent stem cells into -cells: Potential and challenges, Best Pract. Res. Clin. Endocrinol. Metab, vol.29, pp.8-847

J. Rahier, Y. Guiot, R. M. Goebbels, C. Sempoux, and J. C. Henquin, Pancreatic betacell mass in European subjects with type ? diabetes, Diabetes Obes Metab, vol.10

P. Ravassard, Y. Hazhouz, S. Pechberty, E. Bricout-neveu, M. Armanet et al., A genetically engineered human pancreatic cell line exhibiting glucose-inducible insulin secretion, J Clin Invest, vol.121, pp.589-597

G. M. Reaven, Role of insulin resistance in human disease, Diabetes, vol.37, pp.1595-1607, 1988.

A. Rezania, J. E. Bruin, P. Arora, A. Rubin, I. Batushansky et al.,

R. H. Rice and H. Green, , 1977.

S. Rieck, P. White, J. Schug, A. J. Fox, O. Smirnova et al., The transcriptional response of the islet to pregnancy in mice, Mol. Endocrinol, vol.23, issue.?009, pp.170-171

C. K. Roy, J. K. Ojha, and H. S. Bajpai, A review of the history of prameha and diabetes mellitus, Anc. Sci. Life, vol.12, pp.94-98

J. Rui, S. Deng, A. Arazi, A. L. Perdigoto, Z. Liu et al., Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice, Cell Metab, vol.25, pp.7-7

M. F. Saad, W. C. Knowler, D. J. Pettitt, R. G. Nelson, D. M. Mott et al., , 1989.

Y. Saisho, A. E. Butler, E. Manesso, D. Elashoff, R. A. Rizza et al., ?01?). -Cell mass and turnover in humans: Effects of obesity and aging, Diabetes Care, vol.36, pp.111-117

H. Sakuraba, H. Mizukami, N. Yagihashi, R. Wada, C. Hanyu et al., Reduced beta-cell mass and expression of oxidatibe stress-related DNA damage in the islet of Japanese Type II diabetic patients, Diabetologia, vol.45, pp.85-96

L. S. Satin, P. C. Butler, J. Ha, and A. S. Sherman, Pulsatile insulin secretion, impaired glucose tolerance and type ? diabetes, Mol Aspects Med, vol.42, pp.61-77

H. Schatz, N. Katsilambros, C. Nierle, and E. E. Pfeiffer, The effect of biguanides on secretion and biosynthesis of insulin in isolated pancreatic islets of rats, Diabetologia, vol.8, pp.40-407

D. L. Schmucker and H. Sachs, Quantifying dense bodies and lipofuscin during aging: A morphologist's perspective, Arch Gerontol Geriatr, vol.34, pp.49-61

T. Scholzen and J. Gerdes, The Ki-67 protein: From the known and the unknown, J Cell Physiol, vol.182, p.11

J. Schrader, W. Rennekamp, U. Niebergall, M. Schoppet, H. Jahr et al.,

A. Segerstolpe, A. Palasantza, P. Eliasson, E. Andersson, A. Andreasson et al., Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type ? Diabetes, Cell Metab, vol.24, pp.59-607

P. A. Seymour, Sox9: A master regulator of the pancreatic program, Rev. Diabet. Stud, vol.11, pp.51-59

P. A. Seymour, K. K. Freude, C. L. Dubois, H. P. Shih, N. A. Patel et al., A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation, Dev Biol, vol.323, pp.19-19

P. Seymour, K. K. Freude, M. N. Tran, E. E. Mayes, J. Jensen et al., SOX9 is required for maintenance of the pancreatic progenitor cell pool, Proc Natl Acad Sci U S A, vol.104, pp.1865-1870

P. Seymour, H. P. Shih, N. Patel, K. K. Freude, R. Xie et al.,

, A Sox9/Fgf feed-forward loop maintains pancreatic organ identity, Development, vol.139, pp.6-7

K. L. Spalding, R. D. Bhardwaj, B. A. Buchholz, H. Druid, and J. Frisén, Retrospective birth dating of cells in humans, Cell, vol.122, pp.1-14

S. Steven, K. G. Hollingsworth, P. K. Small, S. A. Woodcock, A. Pucci et al., Weight Loss Decreases Excess Pancreatic Triacylglycerol Specifically in Type ? Diabetes, Diabetes Care, vol.39, pp.158-165

D. A. Stoffers, N. T. Zinkin, V. Stanojevic, W. L. Clarke, and J. F. Habener, , 1997.

M. Stumvoll, B. J. Goldstein, and T. W. Van-haeften, Type ? diabetes: Principles of pathogenesis and therapy, Lancet, vol.365, pp.1-1

J. M. Suh, J. W. Jonker, M. Ahmadian, R. Goetz, D. Lackey et al., Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer, Nature

B. A. Sullivan, J. Hollister-lock, S. Bonner-weir, and G. C. Weir, )human -CElls, Diabetes, vol.64, issue.?015, pp.1698-170
URL : https://hal.archives-ouvertes.fr/hal-01833113

X. Sun, X. Fu, W. Han, Y. Zhao, H. Liu et al., Dedifferentiation of human terminally differentiating keratinocytes into their precursor cells induced by basic fibroblast growth factor, Biol Pharm Bull, vol.34, pp.10-17

K. Suzuki, N. Mitsutake, V. Saenko, M. Suzuki, M. Matsuse et al.,

A. Swisa, D. Avrahami, N. Eden, J. Zhang, E. Feleke et al., PAX6 maintains cell identity by repressing genes of alternative islet cell types, J Clin Invest, vol.127, issue.?017, pp.0-4

M. Szabat, F. C. Lynn, B. G. Hoffman, T. J. Kieffer, D. W. Allan et al.,

, Maintenance of beta-cell maturity and plasticity in the adult pancreas: developmental biology concepts in adult physiology, Diabetes, vol.61, pp.1-65

C. Talchai, S. Xuan, H. V. Lin, L. Sussel, A. et al., , p.1

R. Taylor, Aetiology of non-insulin dependent diabetes, Br Med Bull, vol.45, pp.7-91, 1989.

, Health Effects of Overweight and Obesity in 195 Countries over ?5 Years, The GBD ?015 Obesity Collaborators (?017), vol.377, pp.1-7

R. C. Turner, C. A. Cull, V. Frighi, and R. R. Holman, Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type ? diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group, JAMA, vol.281, pp.5-6, 1999.

M. E. Tushuizen, M. C. Bunck, P. J. Pouwels, S. Bontemps, J. H. Van-waesberghe et al., Pancreatic fat content and beta-cell function in men with and without type ? diabetes, Diabetes Care, vol.30, pp.916-925

U. K. , Prospective Diabetes Study (1995). U.K. Prospective diabetes study 16: Overview of 6 years' therapy of type II diabetes: A progressive disease, Diabetes, vol.44, pp.1-49

, UK prospective diabetes study (UKPDS) -VIII. Study design, progress and performance, UKPDS study, vol.34, pp.877-890, 1991.

P. Vague and J. P. Moulin,

A. De-vos, H. Heimberg, E. Quartier, P. Huypens, L. Bouwens et al., Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression, J Clin Invest, vol.96, pp.489-495, 1995.

C. H. Waddington, Organisers & genes, 1940.

C. H. Waddington, The strategy of the genes. A discussion of some aspects of theoretical biology, 1957.

S. Wang, G. M. Beattie, M. I. Mally, V. Cirulli, P. Itkin-ansari et al.,

F. Levine, Isolation and characterization of a cell line from the epithelial cells of the human fetal pancreas, Cell Transplant, vol.6, pp.59-67, 1997.

S. Wang, Q. Yang, S. Yu, R. Pan, D. Jiang et al.,

Z. Wang, N. W. York, C. G. Nichols, and M. S. Remedi, Pancreatic cell dedifferentiation in diabetes and redifferentiation following insulin therapy, Cell Metab, vol.19, pp.87-88

C. Wasserfall, H. S. Nick, M. Campbell-thompson, D. Beachy, L. Haataja et al., Persistence of Pancreatic Insulin mRNA Expression and Proinsulin Protein in Type 1 Diabetes Pancreata, Cell Metab, vol.26, issue.?017, pp.568-575

N. Weinberg, L. Ouziel-yahalom, S. Knoller, S. Efrat, and Y. Dor, Lineage tracing evidence for in-vitro dedifferentiation, but rare proliferation, of mouse pancreatic cells, Diabetes, vol.56

G. C. Weir, Which comes first in non-insulin-dependent diabetes mellitus: insulin resistance or beta-cell failure? Both come first, JAMA, vol.273, pp.1878-1879, 1995.

G. C. Weir and S. Bonner-weir, Finally! A human pancreatic cell line, J Clin Invest, vol.121, pp.95-97

C. Weyer, C. Bogardus, D. M. Mott, and R. E. Pratley, , 1999.

, Global Report on Diabetes (World Health Organization)

R. Xie, L. J. Everett, H. W. Lim, N. A. Patel, J. Schug et al.,

Y. Yamashita-sugahara, M. Matsumoto, M. Ohtaka, K. Nishimura, M. Nakanishi et al., An inhibitor of fibroblast growth factor receptor-1 (FGFR1) promotes late-stage terminal differentiation from NGN?+ pancreatic endocrine progenitors, Sci. Reports, vol.6, p.5908

K. H. Yoon, S. H. Ko, J. H. Cho, J. M. Lee, Y. B. Ahn et al., Selective beta-cell loss and alpha-cell expansion in patients with type ? diabetes mellitus in Korea, J Clin Endocrinol Metab, vol.88, pp.0-08

G. Zhou, R. Myers, Y. Li, Y. Chen, X. Shen et al., Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action, cell Mass in Nondiabetic Autoantibody-Positive Subjects: An Analysis Based on the Network for Pancreatic Organ Donors Database, vol.108, p.75014

J. S. Kirkegaard, , vol.1

N. Nordisk, A. Måløv, and . Denmark, Biotechnology and Biotherapy Team, vol.7225, issue.3

P. Endocells, I. Entreprises, F. Paris, . S. Authorship-note:-j, P. S. Kirkegaard et al., Conflict of interest: P. Ravassard and R. Scharfmann are shareholders and consultants of Endocells. E. Bricout-Neveu is an employee of Endocells, J Clin Invest, vol.Accepted, issue.3, pp.1109-1113, 2015.

, Author Affiliations: 1 INSERM U1016, vol.4, 2002.

P. Cité and F. , ARC Centre of Excellence in Advanced Molecular Imaging, 5 Infection and Immunity Program and Department of Biochemistry and Molecular Biology, vol.4

P. Immunology and . Doherty,

, TrialNet Clinical Center

G. Endocrinologie and D. Pédiatrique,

M. Paris-descartes, Author Notes: * O. Rouxel, § J. DaSilva and L, 11 INSERM U932, Institut Curie

, Corresponding Author: Agnès Lehuen, INSERM 1016, Institut Cochin