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The Making of Pancreatic β Cells: Advances and Apprehensions

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Abstract:

Diabetes is a dreadful disease, which in its acute stages, causes severe multiple organ failure. It is also one of the world’s oldest diseases. Type 1 Diabetes is characterized by the absence of insulin and exogenous insulin dependency. Stem cell therapy is one of the promises of this era, as there are numerous studies on Rodents, Frogs, Zebra fish, Dog and Chick, elucidating the wide array of genes, transcription factors, signaling pathways and compounds, which could promote β cell neogenesis, regeneration, differentiation and trans-differentiation. Even though, a recent PubMed search on the keyword ‘Pancreatic beta cell proliferation’ revealed around 3000 reports, this review focuses on the trends attempted in recent years and infers certain critical aspects in the observations.

Info:

Periodical:
International Journal of Pharmacology, Phytochemistry and Ethnomedicine (Volume 5)
Pages:
34-51
Citation:
B. Radha et al., "The Making of Pancreatic β Cells: Advances and Apprehensions", International Journal of Pharmacology, Phytochemistry and Ethnomedicine, Vol. 5, pp. 34-51, 2016
Online since:
Oct 2016
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[1] C. Pontremoli et al., Natural Selection at the Brush-Border: Adaptations to Carbohydrate Diets in Humans and Other Mammals, Genome Biol Evol. 7 (2015) 2569–2584.

[2] G.T. Cocks, J. Aguilar, E.C.C. Lin, Evolution of L-1, 2-Propanediol Catabolism in Escherichia coli by Recruitment of Enzymes for L-Fucose and L-Lactate Metabolism, J. Bacteriol. 118 (1974) 83–88.

[3] E. Vilanova et al., Carbohydrate-Carbohydrate Interactions Mediated by Sulfate Esters and Calcium Provide the Cell Adhesion Required for the Emergence of Early Metazoans, J. Biol. Chem. 291 (2016) 9425-37.

[4] D.S. Kim, Y. Hahn, The acquisition of novel N-glycosylation sites in conserved proteins during human evolution, BMC Bioinformatics. 16 (2015) 1–12.

[5] P. Zangoui, K. Vashishtha, S. Mahadevan, Evolution of Aromatic β- Glucoside Utilization by Successive Mutational Steps in Escherichia coli, J. Bacteriol. 197 (2015) 710–716.

[6] W.H.T. Loh et al., Intermediary Carbon Metabolism of Azospirillum brasilense, J. Bacteriol. 158 (1984) 264–268.

[7] B.A. Mcfadden, Autotrophic CO2 Assimilation and the Evolution of Ribulose Diphosphate Carboxylase, Bacteriol. Rev. 37 (1973) 289–319.

[8] P.W. Postmal, J.W. Lengeler, Phosphoenolpyruvate : Carbohydrate Phosphotransferase System of Bacteria, Microbiol. Rev. 49 (1985) 232–269.

[9] C. Braga et al., Biochemical and genetic diversity of carbohydrate-fermenting and obligate amino bacteria from Nellore steers fed tropical forages and supplemented with casein, BMC Microbiol. 15 (2015) 1–15.

DOI: https://doi.org/10.1186/s12866-015-0369-9

[10] R.B. Hespell, Glucose and Pyruvate Metabolism of Spirochaeta litoralis, an Anaerobic Marine Spirochete, J. Bacteriol. 116 (1973) 931–937.

[11] A. Barve et al., Historical contingency and the gradual evolution of metabolic properties in central carbon and genome-scale metabolisms, BMC Syst. Biol. 8 (2014) 1–20.

[12] K.B. Walsh, J.K. Vessey, D.B. Layzell, Carbohydrate Supply and N2 Fixation in Soybean, Plant Physiol. 85 (1987) 137–144.

DOI: https://doi.org/10.1104/pp.85.1.137

[13] M.C. De Mares et al., Horizontal transfer of carbohydrate metabolism genes into ectomycorrhizal Amanita, New Phytol. 205 (2015) 1552–1564.

[14] S.V. Holle, E.J.M. Van Damme, Distribution and Evolution of the Lectin Family in Soybean (Glycine max), Molecules. 20 (2015) 2868–2891.

[15] A.R. Timme-laragy et al., Deviant development of pancreatic beta ells from embryonic exposure to PCB-126 in Zebra fish, Comp. Biochem. Physiol. (2015) 1-8.

[16] O. Soliman, Diabetes Mellitus in Egypt in Short, J. Diabetes Metab. 4 (2013) 1-2.

[17] Global status report on Non-communicable diseases 2014, Geneva, World Health Organization, (2012).

[18] S. Wild et al., Estimates for the year 2000 and projections for 2030, Diabetes Care. 27 (2004) 1047–1053.

[19] C.J. Adler et al., Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions, Nat. Genet. 45 (2014) 450–5.

[20] J.Y. Kim et al., Chronic alcohol consumption potentiates the development of diabetes through pancreatic - β cell dysfunction, World J. Biol. Chem. 6 (2015) 1-15.

[21] C.A. Thaiss et al., Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis, Cell. 159 (2014) 514–529.

[22] C. Dong et al., Regulation of transforming growth factor beta1 (TGF-β1)-induced pro-fibrotic activities by circadian clock gene BMAL1, Respir Res. 17 (2016) 1-17.

[23] H. Li et al., The clock gene PER1 suppresses expression of tumor-related genes in human oral Squamous cell carcinoma, Oncotarget. 7 (2016) 22–24.

[24] N.M. Kettner, C.A. Katchy, L. Fu, Circadian gene variants in cancer, Ann. Med. 46 (2015) 208–220.

[25] G. Mazzoccoli et al., Circadian clock circuitry in colorectal cancer, World J. Gastroenterol. 20 (2014) 4197–4207.

[26] P. Bouchard-Cannon et al., The Circadian Molecular Clock Regulates Adult Hippocampal Neurogenesis by Controlling the Timing of Cell-Cycle Entry and Exit, Cell Rep. 5 (2013) 961–973.

[27] E.J. Shields et al., Extreme Beta-Cell Deficiency in Pancreata of Dogs with Canine Diabetes, PLoS ONE. 10 (2015) 1–19.

[28] T.G. Ramsay, M.E. White, C.K. Wolverton., The Onset of Maternal Diabetes in Swine Induces Alterations in the Development of the Fetal Pre-adipocyte, Journal of Animal Sciences. 73 (1995) 69-76.

DOI: https://doi.org/10.2527/1995.73169x

[29] L. Shi et al., Chicken Embryos as a Potential New Model for Early Onset Type I Diabetes, J. Diabetes Res. 2014 (2014) 1-10.

[30] R.W. Nelson, C.E. Reusch, Classification and etiology of Diabetes in Dogs and Cats, J. Endocrinol. 222 (2014) T1–T9.

[31] L. Chen et al., Impact of caffeine on β cell proliferation and apoptosis under the influence of palmitic acid, Genet. Mol. Res. 14 (2015) 5724–5730.

[32] S.K. Abunasef, H.A. Amin, G.A. Abdel-hamid, A Histological and Immunohistochemical study of beta cells in streptozotocin diabetic rats treated with caffeine, Folia Histochem. Cytobiol. 52 (2014) 42–50.

[33] V. Cardinale et al., Adult Human Biliary Tree Stem Cells Differentiate to β-Pancreatic Islet Cells by Treatment with a Recombinant Human Pdx1 Peptide, PLoS ONE. 10 (2015) 1–15.

[34] I. Gesmundo et al., Obestatin: A New Metabolic Player in the Pancreas and White Adipose Tissue, International Union of Biochemistry and Molecular Biology. 65 (2013) 976–982.

DOI: https://doi.org/10.1002/iub.1226

[35] D. Pezzolla et al., Resveratrol Ameliorates the Maturation Process of β -Cell-Like Cells Obtained from an Optimized Differentiation Protocol of Human Embryonic Stem Cells, PLoS ONE. 10 (2015) 1–21.

DOI: https://doi.org/10.1371/journal.pone.0119904

[36] H. Yin et al., Enhancing Pancreatic Beta-Cell Regeneration In Vivo with Pioglitazone and Alogliptin, PLoS ONE. 8(2013) 2–9.

[37] A. Jurczyk, P. DiIorio, D. Brostowin et al., Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2rγnull mice treated with Alogliptin, Diabetes Metab Syndr Obes. 6 (2013) 493–499.

DOI: https://doi.org/10.2147/dmso.s53154

[38] M. Mirjana et al., Protective Effects of the Mushroom Lactarius deterrimus Extract on Systemic Oxidative Stress and Pancreatic Islets in Streptozotocin-Induced Diabetic Rats, J. Diabetes Res. 2015 (2015) 1-10.

[39] U.G. Bhat, V. Ilievski, T.G. Unterman, Porphyromonas Gingivalis Lipopolysaccharide (Pg-LPS) Upregulates Insulin Secretion From Pancreatic Beta Cell Line MIN6, J. Periodontol. (2014) 1–14.

[40] Á. González-rodríguez et al., Essential role of Protein tyrosine phosphatase 1b, In Obesity-induced inflammation and peripheral Insulin Resistance during Aging, Aging Cell. 11(2012) 284–296.

DOI: https://doi.org/10.1111/j.1474-9726.2011.00786.x

[41] S. Liu et al., Disruption of Protein-Tyrosine Phosphatase 1B Expression in the Pancreas Affects β-Cell Function, Endocrinology. 155 (2014) 3329–3338.

[42] N. Dadheech et al., Swertisin an Anti-Diabetic Compound Facilitate Islet Neogenesis from Pancreatic Stem / Progenitor Cells via p-38 MAP Kinase- SMAD Pathway: An In-Vitro and In-Vivo Study, PLoS ONE. 1(2015) 1–21.

[43] N. Rohatgi et al., Novel Insulin Sensitizer Modulates Nutrient Sensing Pathways and Maintains β -Cell Phenotype in Human Islets, PLoS ONE. 8 (2013) 1-13.

[44] L. Quintana-lopez et al., Nitric Oxide Is a Mediator of Antiproliferative Effects Induced by Proinflammatory Cytokines on Pancreatic Beta Cells, Mediators Inflamm. 2013 (2013) 1-10.

[45] H. Jiang et al., The Soybean Peptide Vglycin Preserves the Diabetic β -cells through Improvement of Proliferation and Inhibition of Apoptosis, Nature. 5 (2015) 1–16.

[46] S.B. Stephens et al., A VGF-derived peptide attenuates development of type 2 diabetes via enhancement of islet β-cell survival and function, Cell Metab. 16 (2013) 33–43.

[47] J. Mahadevan et al., Ebselen Treatment Prevents Islet Apoptosis, Maintains Intranuclear Pdx-1 and MafA Levels, and Preserves β -Cell Mass and Function in ZDF Rats, Diabetes. 62 (2013) 3582–3588.

[48] T. Izumoto-akita et al., Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β -cell function, BMJ Open Diabetes Res. Care. 3 (2015) 1–9.

[49] F. Lo et al., Epoxypukalide Induces Proliferation and Protects against Cytokine-Mediated Apoptosis in Primary Cultures of Pancreatic β –Cells, PLoS ONE. 8 (2013) 1–10.

[50] I. Kim et al., Differential Gene Expression in GPR40-Overexpressing Pancreatic β -cells Treated with Linoleic Acid, Korean J. Physiol. Pharmacol. 19 (2015)141–9.

[51] B.W. Lee et al., Enhanced Gene Transfer to Pancreatic Islets Using Glucagon-like Peptide-1, Transplant Proc. 45 (2013) 591–596.

[52] Y. Lu et al., Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor, PLoS ONE. 8 (2013) 1-11.

[53] M. Jose et al., Dopamine Modulates Insulin Release and Is Involved in the Survival of Rat Pancreatic Beta Cells, PLoS ONE. 10(4) (2015) 1–16.

[54] J. Tian et al., γ -Aminobutyric Acid Regulates Both the Survival and Replication of Human β Cells, Diabetes. 62 (2013) 3760-3765.

[55] B. Chandravanshi, A. Dhanushkodi, R. Bhonde, High Recovery of Functional Islets Stored at Low and Ultralow Temperatures, Rev. Diabet. Stud. 11 (2014) 267–278.

[56] R. Ye et al., Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β -cell regeneration, eLife. 3 (2014) 1–21.

[57] A.E.R. Rodríguez et al., Glucose homeostasis changes and pancreatic β -cell proliferation after switching to cyclosporin in Tacrolimus-induced Diabetes mellitus, Nefrologia. 5 (2016) 264–72.

[58] W. Shen et al., Inhibition of DYRK1A and GSK3B induces humanβ -cell proliferation, Nature. 6 (2015) 1–11.

[59] H.H. Hansen et al., The Sodium Glucose Cotransporter Type 2 Inhibitor Empagliflozin Preserves β -Cell Mass and Restores Glucose Homeostasis in the Male Zucker Diabetic Fatty Rat, J. Pharmacol. Exp. Ther. 350 (2014) 657–664.

[60] S. Missaoui et al., Vanadyl Sulfate Treatment Stimulates Proliferation and Regeneration of Beta Cells in Pancreatic Islets, J. Diabetes Res. 61 (2014) 1–7.

[61] T. Shinjo et al., High-fat diet feeding significantly attenuates anagliptin-induced regeneration of islets of Langerhans in streptozotocin-induced diabetic mice, Diabetol. Metab. Syndr. 7 (2015) 1–6.

[62] N. Téllez, E. Montanya, Gastrin induces ductal cell dedifferentiation and β cell neogenesis after 90% Pancreatectomy, J. Endocrinol. 223 (2014) 67–78.

[63] W. Fu et al., Epigenetic modulation of type-1 diabetes via a dual effect on pancreatic macrophages and β cells, eLife. 3 (2014) 31-20.

[64] B.P. Boerner et al., WS6 induces both alpha and beta cell proliferation without affecting differentiation or viability, Endocrine Journal. 62 (2015) 379–386.

[65] N. Tsuji et al., Whole Organism High Content Screening Identifies Stimulators of Pancreatic Beta-Cell Proliferation, PLos ONE. 9 (2014) 1-9.

[66] O. Andersson et al., Adenosine signaling promotes regeneration of pancreatic β-cells In vivo, Cell Metab. 15 (2012) 885–894.

[67] E. Akinci et al., Reprogramming of Various Cell Types to a Beta-Like State by Pdx1, Ngn3 and MafA, PLoS ONE. 8(11) (2013).

[68] Y.J. Kim et al., Transforming Growth Factor Beta Receptor I Inhibitor Sensitizes Drug-resistant Pancreatic Cancer Cells to Gemcitabine, Anticancer Res. 32 (2012) 799–806.

[69] C. Neuzillet et al., Perspectives of TGF-β inhibition in Pancreatic and Hepatocellular Carcinomas, Oncotarget. (2013) 1-17.

[70] T. Suzuki et al., TGF- β Signaling Regulates Pancreatic β- Cell Proliferation through Control of Cell Cycle Regulator p.27 Expression, Acta Histochem Cytochem. 46 (2013) 51–58.

[71] B.P. Boerner et al., TGF-β Superfamily Member Nodal Stimulates Human β -Cell Proliferation While Maintaining Cellular Viability, Endocrinology. 154 (2013) 4099–4112.

DOI: https://doi.org/10.1210/en.2013-1197

[72] E.D. Bernardini et al., Endothelial Lineage Differentiation from Induced Pluripotent Stem Cells Is Regulated by MicroRNA-21 and Transforming Growth Factor β2 (TGF-β2) Pathways, J. Biol. Chem. 289 (2014) 3383–3393.

[73] H. Ishigame et al., Excessive Th1 responses due to the absence of TGF- β signaling cause autoimmune diabetes and dysregulated Treg cell homeostasis, Proc. Natl. Acad. Sci. 110 (2013) 6961–6966.

DOI: https://doi.org/10.1073/pnas.1304498110

[74] X. Xiao et al., No evidence for β cell neogenesis in murine adult pancreas, J. Clin. Invest. 123 (2013) 2207–2217.

[75] Y. El-gohary et al., A Smad Signaling Network Regulates Islet Cell Proliferation, The American Diabetes Association. 63 (2014) 224–236.

[76] G. Toren-haritan, S. Efrat, TGF β Pathway Inhibition Redifferentiates Human Pancreatic Islet β Cells Expanded In Vitro, PLoS ONE. 10 (2015) 1–17.

[77] E.K. Colvin et al., Retinoid Signaling in Pancreatic Cancer, Injury and Regeneration, PLoS ONE. 6 (2011) 1-10.

[78] G. Pennarossa et al., Brief demethylation step allows the conversion of adult human skin fibroblasts into insulin-secreting cells, Proc. Natl. Acad. Sci. 110 (2013) 1–6.

[79] M. Paschaki et al., Retinoic acid regulates olfactory progenitor cell fate and differentiation Retinoic acid regulates olfactory progenitor cell fate and differentiation, Neural Dev. 8 (2013) 1-10.

[80] C. Talchai et al., Pancreatic β-Cell Dedifferentiation As Mechanism Of Diabetic β- Cell Failure, Cell. 150 (2012) 1223–1234.

[81] S. Marshak et al., β -Cell–Specific Expression of Insulin and PDX-1 Genes, Diabetes. 50 (2001) 131–132.

[82] C. Delisle et al., Pdx-1 or Pdx-1-VP16 protein transduction induces β-cell gene expression in liver-stem WB cells, BMC Res Notes. 8 (2009) 1–8.

[83] M. Bahrebar et al., Generation of Islet-like Cell Aggregates from Human Adipose Tissue-derived Stem Cells by Lentiviral Overexpression of PDX-1, Int. J. Organ. Transplant. Med. 6 (2015) 61-76.

[84] S. Yoshida et al., PDX-1 Induces Differentiation of Intestinal Epithelioid IEC-6 Into Insulin-Producing Cells, Diabetes. 51 (2002) 2505–2513.

[85] M. Koizumi et al., Forced expression of PDX-1 induces insulin production in intestinal epithelia, Surgery. 140 (2006) 273-280.

[86] H. Wang et al., Characterization of insulin-producing cells derived from PDX-1-transfected neural stem cells, Mol. Med. Rep. 6 (2012) 1428-1432.

[87] H.L. Hayes et al., Pdx-1 Activates Islet α - and β -Cell Proliferation via a Mechanism Regulated by Transient Receptor Potential Cation Channels 3 and 6 and Extracellular Signal-Regulated Kinases 1 and 2, Mol. Cell Biol. 33 (2013) 4017–29.

[88] A.M. Holland et al., The Parahox gene Pdx1 is required to maintain positional identity in the adult foregut, Int. J. Dev. Biol. 398 (2013) 391–398.

[89] R.A. Kimmel et al., Diabetic pdx-1 mutant zebra fish show conserved responses to nutrient overload and anti- glycemic treatment, Nature. 5 (2015) 1–14.

[90] D. Oropeza, M. Horb, Transient expression of Ngn3 in Xenopus endoderm promotes early and ectopic development of pancreatic beta and delta cells, Genesis. 50 (2012) 271–285.

[91] M.V. Casteele et al., Neurogenin-3+ ve cells contribute to β -cell neogenesis and proliferation in injured adult mouse pancreas, Cell Death Dis. 4 (2013) 1–11.

[92] D.L. Gomez et al., Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate, PLoS ONE. 10 (2015) 1–26.

[93] E. Markljung et al., ZBED6, a Novel Transcription Factor Derived from a Domesticated DNA Transposon Regulates IGF2 Expression and Muscle Growth, PLos Biology. 7 (2009) 1-13.

[94] X. Wang et al., Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells, Proc. Natl. Acad. Sci. 110 (2013) 5997–6002.

[95] P. Collombat et al., Opposing actions of Arx and Pax4 in endocrine pancreas development, Genes Dev. 17 (2003) 2591–2603.

[96] P. Collombat et al., Embryonic endocrine pancreas and mature β cells acquire α and PP cell phenotypes upon Arx misexpression, J. Clin. Invest. 117 (2007) 961–970.

[97] J. Djiotsa et al., Pax4 is not essential for beta-cell differentiation in zebrafish embryos but modulates alpha-cell generation by repressing arx gene expression, BMC Dev. Biol. 12 (2012) 1-16.

[98] P.I. Lorenzo et al., PAX4 Defines an Expandable β -Cell Subpopulation in the Adult Pancreatic Islet, Nature. 5 (2015) 1–14.

[99] N. Okamoto, Y. Nishimori, T. Nishimura, Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression, Proc. Natl. Acad. Sci. 109 (2012) 2406–2411.

[100] M.R. Metukuri et al., ChREBP Mediates Glucose-Stimulated Pancreatic β -Cell Proliferation, Diabetes. 61 (2012) 2012-(2015).

[101] R.E. Stamateris et al., Adaptive β -cell proliferation increases early in high-fat feeding in mice , concurrent with metabolic changes , with induction of islet cyclin D2 expression, Am. J. Physiol. Endocrinol. Metab. 305 (2013) 149–159.

[102] W.R. Goodyer et al., Neonatal β Cell Development in Mice and Humans Is Regulated by Calcineurin/NFAT, Dev. Cell. 23 (2012) 21–34.

[103] W.P. Kloosterman, R.H.A. Plasterk, The Diverse Functions of MicroRNAs in Animal Development and Disease, Dev. Cell. 11 (2006) 441–450.

[104] K. Tugay et al., Role of microRNAs in the age-associated decline of pancreatic beta cell function in rat islets, Diabetologia. 59 (2016) 161–169.

[105] H.Y. Jin et al., Transfection of microRNA Mimics Should Be Used with Caution, Front. Genet. 6 (2015) 1-23.

[106] S. Kredo-Russo et al., Pancreas-enriched miRNA refines endocrine cell differentiation, Development. 139(16) (2012) 3021–3031.

[107] M.N. Poy et al., miR-375 maintains normal pancreatic α - and β -cell mass, Proc. Natl. Acad. Sci. 106 (2009) 5813–5818.

[108] T. Avnit-sagi, T. Vana, M.D. Walker, Transcriptional Mechanisms Controlling miR-375 Gene Expression in the Pancreas, Exp. Diabetes Res. 2012 (2012) 1-5.

[109] D.M. Keller, E.A. Clark, R.H. Goodman, Regulation of microRNA-375 by cAMP in Pancreatic β-Cells, Mol. Endocrinol. 26 (2012) 989–999.

[110] G. Nathan et al., MiR-375 Promotes Redifferentiation of Adult Human β Cells Expanded In Vitro, PLoS ONE. 10 (2015) 1–18.

[111] Y. Lu et al., Glucose-induced microRNA-17 promotes pancreatic beta cell proliferation through down-regulation of Menin, Eur. Rev. Med. Pharmacol. Sci. 19 (2015) 624–629.

[112] Y. Zhou et al., MiR-17 ~ 92 ablation impairs liver regeneration in an estrogen-dependent manner, J. Cell Mol. Med. 20 (2016) 939–948.

[113] M. Mihailovich, T. Bonaldi, MS-analysis of SILAC-labeled MYC-driven B lymphoma cells overexpressing miR-17-19b, Data Brief. 7 (2016) 349–353.

[114] J. Wu, K. Du, X. Lu, Elevated expressions of serum miR-15a, miR-16, and miR-17-5p are associated with acute ischemic stroke, Int. J. Clin. Exp. Med. 8 (2015) 21071–21079.

[115] N.V. Conev et al., Potential biomarkers for recurrence after adjuvant chemotherapy in Colon cancer patients, Biosci Trends. 9 (2015) 393–401.

[116] D.R. Bhandari et al., The Simplest method for in vitro β-cell production from human adult stem cells, Differentiation. 82(2011) 144–152.

[117] N. Lumelsky et al., Differentiation of embryonic stem cells to insulin- secreting structures similar to pancreatic islets, Science. 292 (2001) 1389-1394.

[118] Y. Shi et al., Inducing Embryonic Stem Cells to Differentiate into Pancreatic β Cells by a Novel Three-Step Approach with Activin A and All-Trans Retinoic Acid, Stem Cells. 23 (2005) 656–662.

[119] K.A. D'Amour et al., Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells, Nat. Biotechnol. 11 (2006) 1392-1401.

[120] J. Jiang et al., Generation of Insulin-Producing Islet-Like Clusters from Human Embryonic Stem cells, Stem Cells. 25 (2007) 1940–(1953).

[121] S. Toivonen et al., Comparative Analysis of Targeted Differentiation of Human Induced Pluripotent Stem Cells (hiPSCs) and Human Embryonic Stem Cells Reveals Variability Associated With Incomplete Transgene Silencing in Retrovirally Derived hiPSC Lines, Stem Cells Transl. Med. 2 (2013).

[122] R. Wei et al., Insulin-Producing Cells Derived from Human Embryonic Stem Cells: Comparison of Definitive Endoderm- and Nestin-Positive Progenitor-Based Differentiation Strategies, PLoS ONE. 8 (2013) 1–13.

[123] M.M. Gabr et al., Generation of Insulin-Producing Cells from Human Bone Marrow-Derived Mesenchymal Stem Cells : Comparison of Three Differentiation Protocols, Biomed. Res. Int. 2014 (2014) 1-9.

[124] E.T. Hisanaga et al., A Simple Method to Induce Differentiation of Murine Bone Marrow Mesenchymal Cells to Insulin-producing Cells Using Conophylline and Betacellulin-delta4, Endocr. J. 55 (2008) 535–543.

[125] T. Tayaramma et al., Chromatin-Remodeling Factors Allow Differentiation of Bone Marrow Cells into Insulin-Producing Cells, Stem Cells. 24 (2006) 2858–2867.

[126] M.M. Gabr et al., Insulin-Producing Cells From Adult Human Bone Marrow Mesenchymal Stem Cells Control Streptozotocin-Induced Diabetes In Nude Mice, Cell Transplant. 22 (2013) 133–145.

[127] T. Toyoda et al., Cell aggregation optimizes the differentiation of human ESCs and iPSCs into pancreatic bud-like progenitor cells, Stem Cell Res. 14 (2015) 185–197.

[128] D. Ham et al., Generation of Functional Insulin-Producing Cells from Neonatal Porcine Liver-Derived Cells by PDX1 / VP16, BETA2 / NeuroD and MafA, PLoS ONE. 8 (2013) 23–7.

[129] J. Lee et al., Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells, eLife. 2 (2013) 1–22.

[130] F.S. Samani et al., In Vitro Differentiation of Human Umbilical Cord Blood CD133 + Cells into Insulin Producing Cells in Co-Culture with Rat Pancreatic Mesenchymal Stem Cells, Cell Journal (Yakhteh). 17 (2015) 211–220.

[131] L. Khorsandi, S. Saremy, A. Khodadadi et al., Effects of Exendine-4 on The Differentiation of Insulin Producing Cells from Rat Adipose-Derived Mesenchymal Stem Cells, Cell Journal (Yakhteh). 17 (2016) 720–729.

[132] H. Qu et al., Laminin 411 acts as a potent inducer of umbilical cord mesenchymal stem cell differentiation into insulin-producing cells, J. Transl. Med. 12 (2014) 1–12.

[133] S. Chera et al., Diabetes Recovery By Age-Dependent Conversion of Pancreatic δ-Cells Into Insulin Producers, Nature. 514 (2014) 503–507.

[134] Y. Chen, P.T. Fueger, Z. Wang, Depletion of PAK1 enhances Ubiquitin-mediated Survivin degradation in pancreatic β –cells, Islets. 5 (2013) 22–28.

[135] K. Dammann et al., PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation, Biochem. Biophys. Acta. 1853(10) (2015) 2349–2360.

[136] G. Wang et al., PAK1-mediated MORC2 phosphorylation promotes gastric tumorigenesis, Oncotarget. 6 (2015) 9877-9886.

[137] G. Wang et al., PAK1 regulates RUFY3-mediated gastric cancer cell migration and invasion, Cell Death Dis. 77 (2015) 1–11.

[138] M. Zheng et al., Potentially functional polymorphisms in PAK1 are associated with risk of lung cancer in a Chinese population, Cancer Med. 4 (2015) 1781–1787.

[139] A. Pandolfi et al., PAK1 is a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome, Blood. 126 (2015) 1118–1127.

[140] J. Nakae et al., Regulation of insulin action and pancreatic beta- cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1, Nat. Genet. 32 (2002) 245-253.

[141] J. Buteau et al., Metabolic Diapause in Pancreatic β -Cells Expressing a Gain-of-function Mutant of the Forkhead Protein Foxo1, J. Biol. Chem. 282 (2007) 287–293.

[142] R. Paradis et al., Nov/Ccn3, a Novel Transcriptional Target of FoxO1 Impairs Pancreatic β-Cell Function, PLoS ONE. 8 (2013) 1-8.

[143] G. Pennarossa et al., Brief demethylation step allows the conversion of adult human skin fibroblasts into insulin-secreting cells, Proc. Natl. Acad. Sci. 110 (2013) 1–6.

[144] N.C. Bramswig et al., Epigenomic plasticity enables human pancreatic α to β cell reprogramming, J. Clin. Invest. 23 (2013) 1275–1284.

[145] Y. Saisho et al., β -Cell Mass and Turnover in Humans, Diabetes care. 36 (2013) 111-117.

[146] M. Stolovich-rain et al., Pancreatic Beta Cells in Very Old Mice Retain Capacity for Compensatory Proliferation, J. Biol. Chem. 287 (2012) 27407-27414.

[147] M.M. Rankin, J.A. Kushner, Adaptive β Cell Proliferation Is Severely Restricted With Advanced Age, Diabetes. 58 (2009) 1365-1372.

[148] M.E. Carlson et al., Relative roles of TGF- b 1 and Wnt in the systemic regulation and aging of satellite cell responses, Aging Cell. 8 (2009) 676–689.

[149] S.Y. Song et al., Determination of adipose-derived stem cell application on photo-aged fibroblasts, based on paracrine function, Cytotherapy. 3 (2011) 378-384.

[150] S.A. Villeda et al., The aging systemic milieu negatively regulates neurogenesis and cognitive function, Nature. 477 (2012) 90–94.

[151] S.J. Salpeter et al., Systemic Regulation of the Age-Related Decline of Pancreatic β -Cell Replication, Diabetes. 62 (2013) 2843–2848.

[152] J.X. Zhou et al., Combined modulation of polycomb and trithorax genes rejuvenates β cell replication, J. Clin. Invest. 123 (2013) 4849–4858.

[153] M. Li et al., Targeted Overexpression of CKI-Insensitive Cyclin-Dependent Kinase 4 Increases Functional β-Cell Number Through Enhanced Self-Replication in Zebrafish, Zebrafish. 10 (2013) 170–176.

[154] E. Salas et al., Role of Ink4a / Arf Locus in Beta Cell Mass Expansion under Physiological and Pathological Conditions, J. Diabetes Res. 2014 (2014) 1-7.

[155] S. Naif et al., Ablation of insulin-producing cells prevents obesity but not premature mortality caused by a high-sugar diet in Drosophila, Proc. Biol. Sci. 282 (2014) 1-9.

[156] R.T. Birse et al., Regulation of insulin-producing cells in the adult Drosophila brain via the tachykinin peptide receptor DTKR, J. Exp. Biol. 214 (2011) 4201–4208.

[157] Y. Yu et al., Neuronal Cbl Controls Biosynthesis of Insulin-Like Peptides in Drosophila melanogaster, Mol. Cell Biol. 32 (2012) 3610–3623.

[158] I. Cozar-Castellano et al., Induction of β Cell Proliferation and Retinoblastoma Protein Phosphorylation in Rat and Human Islets Using Adenovirus-Mediated Transfer of Cyclin-Dependent Kinase-4 and Cyclin D1, Diabetes. 53 (2004) 149-159.

[159] N.M. Fiaschi-Taesch et al., Induction of Human β-Cell Proliferation and Engraftment Using a Single G1/S Regulatory Molecule, cdk6, Diabetes. 59 (2010) 1926–(1936).

[160] N.M. Fiaschi-Taesch et al., Human Pancreatic β -Cell G1/S Molecule Cell Cycle Atlas, Diabetes. 62 (2013) 2450–2459.

[161] S. Tiwari et al., Early and Late G1 / S Cyclins and Cdks Act Complementarily to Enhance Authentic Human β -Cell Proliferation and Expansion, Diabetes. 64 (2015) 3485–3498.

[162] A.K. Robitaille et al., High-Throughput Functional Genomics Identifies Regulators Of Primary Human Beta Cell Proliferation, J. Biol. Chem. 29 (2016) 4614-4625.

[163] A. Medina et al., Involvement of the parasympathetic nervous system in the initiation of regeneration of pancreatic β-cells, Endocr. J. 60 (2013) 687–96.

[164] M.M. Feng et al., An autocrine γ-aminobutyric acid signaling system exists in pancreatic β -cell progenitors of fetal and postnatal mice, Int. J. Physiol. Pathophysiol. Pharmacol. 5 (2013) 91–101.

[165] A.V. Biankin et al., Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes, Nature. 491 (2012) 399–405.

[166] B.S. Pourcain et al., Common variation near ROBO2 is associated with expressive vocabulary in infancy, Nat. Commun. 5 (2014) 1–9.

[167] T.A. Evans et al., Robo2 acts in trans to inhibit Slit-Robo1 repulsion in pre-crossing commissural axons, eLife. 4 (2015) 1–26.

[168] G. Harburg et al., SLIT/ROBO2 Signaling Promotes Mammary Stem Cell Senescence by Inhibiting Wnt Signaling, Stem Cell Reports. 3(2014) 385–393.

[169] H.A.N. Al-wadei et al., Celecoxib and GABA Cooperatively Prevent the Progression of Pancreatic Cancer In-Vitro and in Xenograft Models of Stress-Free and Stress-Exposed Mice, PLos ONE. 7 (2012) 1–11.

[170] Y. Chen et al., De Novo Formation of Insulin-Producing Neo - β Cell Islets, from Intestinal Crypts, Cell Rep. 6 (2013) 1046–1058.

[171] R.D. Hickey et al., Generation of islet-like cells from mouse gall bladder by direct ex vivo reprogramming, Stem Cell Res. 11 (2013) 503–515.

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