PPARs, Cell Differentiation, and Glucose Homeostasis

AbstractSome individuals develop prediabetes and/or diabetes following acute pancreatitis (AP). AP-induced beta-cell injury and the limited regenerative capacity of beta cells might account for pancreatic endocrine insufficiency. Previously, we found that only a few pancreatic cytokeratin 5 positive (Krt5+) cells differentiated into beta cells in the murine AP model, which was insufficient to maintain glucose homeostasis. Notch signaling determines pancreatic progenitor differentiation in pancreas development. This study aimed to examine whether Notch signaling inhibition could promote pancreatic Krt5+ cell differentiation into beta cells and improve glucose homeostasis following AP. Pancreatic tissues from patients with acute necrotizing pancreatitis (ANP) were used to evaluate beta-cell injury, Krt5+ cell activation and differentiation, and Notch activity. The murine AP model was induced by cerulein, and the effect of Notch inhibition on Krt5+ cell differentiation was evaluated both in vivo and in vitro. The results demonstrated beta-cell loss in ANP patients and AP mice. Krt5+ cells were activated in ANP pancreases along with persistently elevated Notch activity, which resulted in the formation of massive duct-like structures. AP mice that received Notch inhibitor showed that impaired glucose tolerance was reversed 7 and 15 days following AP, and increased numbers of newborn small islets due to increased differentiation of Krt5+ cells to beta cells to some extent. In addition, Krt5+ cells isolated from AP mice showed increased differentiation to beta cells by Notch inhibition. Collectively, these findings suggest that beta-cell loss contributes to pancreatic endocrine insufficiency following AP, and inhibition of Notch activity promotes pancreatic Krt5+ cell differentiation to beta cells and improves glucose homeostasis. The findings from this study may shed light on the potential treatment of prediabetes/diabetes following AP.

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A Simple Matter of Life and Death—The Trials of Postnatal Beta-Cell Mass Regulation

International Journal of Endocrinology ◽

10.1155/2012/516718 ◽

2012 ◽

Vol 2012 ◽

pp. 1-20 ◽

Cited By ~ 18

Author(s):

Elena Tarabra ◽

Stella Pelengaris ◽

Michael Khan

Keyword(s):

Cell Differentiation ◽

Beta Cell ◽

Glucose Homeostasis ◽

Pancreatic Beta Cells ◽

Cell Mass ◽

Beta Cell Mass ◽

Signalling Pathways ◽

Life And Death ◽

Cell Numbers ◽

Differentiation And Proliferation

Pancreatic beta-cells, which secrete the hormone insulin, are the key arbiters of glucose homeostasis. Defective beta-cell numbers and/or function underlie essentially all major forms of diabetes and must be restored if diabetes is to be cured. Thus, the identification of the molecular regulators of beta-cell mass and a better understanding of the processes of beta-cell differentiation and proliferation may provide further insight for the development of new therapeutic targets for diabetes. This review will focus on the principal hormones and nutrients, as well as downstream signalling pathways regulating beta-cell mass in the adult. Furthermore, we will also address more recently appreciated regulators of beta-cell mass, such as microRNAs.

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Jazf1 acts as a regulator of insulin‐producing β‐cell differentiation in induced pluripotent stem cells and glucose homeostasis in mice

FEBS Journal ◽

10.1111/febs.15751 ◽

2021 ◽

Author(s):

Si Jun Park ◽

Wookbong Kwon ◽

Song Park ◽

Jain Jeong ◽

Dongjun Kim ◽

...

Keyword(s):

Stem Cells ◽

Cell Differentiation ◽

Induced Pluripotent Stem Cells ◽

Glucose Homeostasis ◽

Pluripotent Stem Cells ◽

Β Cell ◽

Induced Pluripotent

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Electron microscope study of the secretory activity of epithelial cells in embryonic thymus

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010015945x ◽

1990 ◽

Vol 48 (3) ◽

pp. 382-383

Author(s):

H. Alasam

Keyword(s):

Cell Differentiation ◽

T Cell ◽

Epithelial Cells ◽

Electron Density ◽

Secretory Activity ◽

T Cell Differentiation ◽

High Electron ◽

Transmission Electron ◽

Medullary Epithelial Cells ◽

Thymic Factor

The possibility that intrathymic T-cell differentiation involves stem cell-lymphoid interactions in embryos led us to study the ultrastructure of epithelial cell in normal embryonic thymus. Studies in adult thymus showed that it produces several peptides that induce T-cell differentiation. Several of them have been chemically characterized, such as thymosin α 1, thymopoietin, thymic humoral factor or the serum thymic factor. It was suggested that most of these factors are secreted by populations of A and B-epithelial cells.Embryonic materials were obtained from inbred matings of Swiss Albino mice. Thymuses were disected from embryos 17 days old and prepared for transmission electron microscopy. Our studies showed that embryonic thymus at this stage contains undifferentiated and differentiated epithelial cells, large lymphoblasts, medium and few small lymphocytes (Fig. 5). No differences were found between cortical and medullary epithelial cells, in contrast to the findings of Van Vliet et al,. Epithelial cells were mostly of the A-type with low electron density in both cytoplasm and nucleus. However few B-type with high electron density were also found (Fig. 7).

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