Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells

Vaca, Pilar; Berná, Genoveva; Araujo, Raquel; Carneiro, Everardo M.; Bedoya, Francisco J.; Soria, Bernat; Martı́n, Franz

doi:10.1016/j.yexcr.2007.11.019

Cited by 57 publications

(40 citation statements)

References 21 publications

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“…36 To confirm this fact, it has been shown that histone deacetylase inhibitors have an important role in mES cell differentiation. [36][37][38] It is interesting to note that Brachyury was highly expressed in control cells without LIF condition, indicating that these cells were committed to differentiation to mesoderm and endoderm. The fact that Brachyury expression was cancelled and Pdx1 and Gata 4 increased by NO treatment indicates that NO favored differentiation to endoderm.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide repression of Nanog promotes mouse embryonic stem cell differentiation

et al. 2010

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Exposure of mouse embryonic stem (mES) cells to high concentrations of chemical nitric oxide (NO) donors promotes differentiation, but the mechanisms involved in this process at the gene expression level are poorly defined. In this study we report that culture of mES cells in the presence of 0.25-1.0 mM diethylenetriamine nitric oxide adduct (DETA-NO) leads to downregulation of Nanog and Oct4, the two master genes involved in the control of the pluripotent state. This action of NO was also apparent in the human ES cell line, HS 181. The suppressive action of NO on Nanog gene depends on the activation of p53 repressor protein by covalent modifications, such as pSer15, pSer315, pSer392 and acetyl Lys 379. NO-induced repression of Nanog is also associated with binding of trimethylated histone H3 and pSer315 p53 to its promoter region. In addition, exposure to 0.5 mM DETA-NO induces early differentiation events of cells with acquisition of epithelial morphology and expression of markers of definitive endoderm, such as FoxA2, Gata4, Hfn1-b and Sox 17. This phenotype was increased when cells were treated with valproic acid (VPA) for 10 days.

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Section: Discussionmentioning

confidence: 99%

Nitric oxide repression of Nanog promotes mouse embryonic stem cell differentiation

et al. 2010

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“…Many attempts have been made in gene therapy for type 1 diabetes mellitus, including islet [17][18][19] and whole pancreas transplantation [20,21] , the regeneration of β cells [22][23][24] , and insulin gene therapy [25][26][27] . Whole organ transplants have been found to be sustainable and durable.…”

Section: Discussionmentioning

confidence: 99%

Expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats

Niu

Xie

et al. 2008

Acta Pharmacol Sin

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Aim: To study the expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats. Methods: pCMV.Ins, an expression plasmid of the human insulin gene, was constructed. In total, 100 μg pCMV.Ins wrapped with chitosan nanoparticles (chitosan-pCMV.Ins) was transfected to NIH3T3 cells and diabetes rats through lavage and coloclysis, respectively. The transfected cells were grown in Dulbecco's modified Eagle's medium, containing G418, for 72 h after transfection. The clones were selected and continued to grow in G418 medium for 24 d. The expression of human insulin was detected by immunohistochemistry. Human insulin in the culture medium of transfected cells was measured. Fasting blood glucose and plasma human insulin of diabetic rats were measured for 5 d after transfection. RT-PCR and Western blotting were performed to confirm the expression of the human insulin gene in diabetic rats. Results: Approximately 10% of NIH3T3 cells transfected by chitosan-pCMV.Ins expressed human insulin. Human insulin in the culture medium of NIH3T3 cells transfected by chitosan-pCMV.Ins significantly increased compared with that of the control group (P<0.01). Fasting blood glucose levels of the lavage group and the coloclysis group decreased significantly in 5 d (P<0.01) in comparison, while plasma insulin levels were much higher (P<0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and the coloclysis groups. Conclusion: The human insulin gene can be transfected and expressed successfully by chitosanpCMV.Ins in NIH3T3 cells and diabetes rats, which indicates that chitosan is a promising, non-viral vector for gene expression.

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“…These advances in our understanding of the signaling pathways and transcription factors that regulate the em-bryonic development of the pancreas have informed efforts to derive glucose-responsive ␤-like cells from human and mouse ES cells (Lumelsky et al 2001;Hori et al 2002;Kim et al 2003;Blyszczuk et al 2004;Vaca et al 2008). For a detailed review of directed differentiation of ES cells to pancreatic endocrine cells, see Spence and Wells (2007).…”

Section: Directed Differentiation Of Es Cellsmentioning

confidence: 99%

On the origin of the β cell

Oliver‐Krasinski¹,

Stoffers²

2008

Genes Dev.

334

320

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The major forms of diabetes are characterized by pancreatic islet ␤-cell dysfunction and decreased ␤-cell numbers, raising hope for cell replacement therapy. Although human islet transplantation is a cell-based therapy under clinical investigation for the treatment of type 1 diabetes, the limited availability of human cadaveric islets for transplantation will preclude its widespread therapeutic application. The result has been an intense focus on the development of alternate sources of ␤ cells, such as through the guided differentiation of stem or precursor cell populations or the transdifferentiation of more plentiful mature cell populations. Realizing the potential for cell-based therapies, however, requires a thorough understanding of pancreas development and ␤-cell formation. Pancreas development is coordinated by a complex interplay of signaling pathways and transcription factors that determine early pancreatic specification as well as the later differentiation of exocrine and endocrine lineages. This review describes the current knowledge of these factors as they relate specifically to the emergence of endocrine ␤ cells from pancreatic endoderm. Current therapeutic efforts to generate insulin-producing ␤-like cells from embryonic stem cells have already capitalized on recent advances in our understanding of the embryonic signals and transcription factors that dictate lineage specification and will most certainly be further enhanced by a continuing emphasis on the identification of novel factors and regulatory relationships.Diabetes is rapidly becoming a global epidemic, with a staggering health, societal, and economic impact. Recent estimates by the American Diabetes Association suggest that the lifetime risk of developing diabetes for Americans born in the year 2000 is one in three. Diabetes results when insulin production by the pancreatic islet ␤ cell is unable to meet the metabolic demand of peripheral tissues such as liver, fat, and muscle.A reduction in ␤-cell function and mass leads to hyperglycemia (elevated blood sugar) in both type 1 and type 2 diabetes. In type 1 diabetes, autoimmune destruction of the ␤ cell itself severely reduces ␤-cell mass, resulting in marked hypoinsulinemia and potentially lifethreatening ketoacidosis. In contrast, during the progression to type 2 diabetes, impaired ␤-cell compensation in the setting of insulin resistance (impaired insulin action) eventually leads to ␤-cell failure and a modest but significant reduction in ␤-cell mass (Maclean and Ogilvie 1955; Butler et al. 2003;Yoon et al. 2003). More recently, autoimmunity has been detected in a subset of patients with type 2 diabetes, which has led to a revision of the classification to include LADA, latent autoimmune diabetes of adulthood, underscoring the continuum between type 1 and type 2 diabetes, and raising questions as to the role of immunity and inflammation in ␤-cell dysfunction and death in type 2 diabetes (Syed et al. 2002; Pozzilli and Buzzetti 2007). Conversely, forms of ketosis prone diabetes due to sev...

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Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells

Cited by 57 publications

References 21 publications

Nitric oxide repression of Nanog promotes mouse embryonic stem cell differentiation

Nitric oxide repression of Nanog promotes mouse embryonic stem cell differentiation

Expression of human insulin gene wrapped with chitosan nanoparticles in NIH3T3 cells and diabetic rats

On the origin of the β cell

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