Glucose-dependent expansion of pancreatic beta-cells by the protein p8 in vitro and in vivo

2007 ◽  
Vol 115 (S 1) ◽  
Author(s):  
G Päth ◽  
A Opel ◽  
M Gehlen ◽  
V Rothhammer ◽  
X Niu ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells

Comparative toxicity of alloxan, N-alkylalloxans and ninhydrin to isolated pancreatic islets in vitro

1997 ◽  
Vol 155 (2) ◽  
pp. 283-293 ◽  
Author(s):  
A Jorns ◽  
R Munday ◽  
M Tiedge ◽  
S Lenzen
Keyword(s):  
Beta Cell ◽  
Pancreatic Islets ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Ultrastructural Changes ◽  
Cell Necrosis ◽  
High Concentrations ◽  
Beta Cell Necrosis

The in vitro toxicity of the diabetogenic agent alloxan as documented by the induction of beta cell necrosis was studied in isolated ob/ob mouse pancreatic islets. The effect of alloxan has been compared with that of a number of N-alkyl alloxan derivatives and with that of the structurally related compound, ninhydrin. Alloxan and its derivatives were selectively toxic to pancreatic beta cells, with other endocrine cells and exocrine parenchymal cells being well preserved, even at high concentration. In contrast, ninhydrin was selectively toxic to pancreatic beta cells only at comparatively low concentration, destroying all islet cell types at high concentrations. The ultrastructural changes induced by all the test compounds in pancreatic beta cells in vitro were very similar to those observed during the development of alloxan diabetes in vivo. The relative toxicity of the various compounds to pancreatic beta cells in vitro was not, however, related to their ability to cause diabetes in vivo. Indeed, the non-diabetogenic substances ninhydrin, N-butylalloxan and N-isobutylalloxan were very much more toxic to isolated islets than the diabetogenic compounds alloxan and N-methylalloxan. These results suggest that the differences in diabetogenicity among alloxan derivatives are not due to intrinsic differences in the susceptibility of the pancreatic beta cells to their toxicity, but may reflect differences in distribution or metabolism. High concentrations of glucose protected islets against the harmful effects of alloxan and its derivatives, but not those of ninhydrin. Low levels of glucose, and non-carbohydrate nutrients, afforded little protection, indicating that the effect of glucose is not due to the production of reducing equivalents within the cell, 3-O-Methylglucose, which protects against alloan diabetes in vivo, did not protect against alloxan toxicity in vitro. Since 3-O-methylglucose is known to prevent uptake of alloxan by pancreatic beta cells, it appears that uptake of alloxan by the cell is not a prerequisite for the induction of beta cell necrosis.

scholarly journals The dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells

2011 ◽  
Vol 22 (13) ◽  
pp. 2235-2245 ◽  
Author(s):  
Zhongyan Zhang ◽  
Nobunao Wakabayashi ◽  
Junko Wakabayashi ◽  
Yasushi Tamura ◽  
Woo-Jin Song ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Electron Transport ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Electron Transport Chain ◽  
Chain Complex ◽  
Atp Production ◽  
Transport Chain

Previous studies using in vitro cell culture systems have shown the role of the dynamin-related GTPase Opa1 in apoptosis prevention and mitochondrial DNA (mtDNA) maintenance. However, it remains to be tested whether these functions of Opa1 are physiologically important in vivo in mammals. Here, using the Cre-loxP system, we deleted mouse Opa1 in pancreatic beta cells, in which glucose-stimulated ATP production in mitochondria plays a key role in insulin secretion. Beta cells lacking Opa1 maintained normal copy numbers of mtDNA; however, the amount and activity of electron transport chain complex IV were significantly decreased, leading to impaired glucose-stimulated ATP production and insulin secretion. In addition, in Opa1-null beta cells, cell proliferation was impaired, whereas apoptosis was not promoted. Consequently, mice lacking Opa1 in beta cells develop hyperglycemia. The data suggest that the function of Opa1 in the maintenance of the electron transport chain is physiologically relevant in beta cells.

scholarly journals Stem Cell Therapy for Diabetes: Beta Cells versus Pancreatic Progenitors

2020 ◽  
Author(s):  
Essam Abdelalim ◽  
Bushra Memon
Keyword(s):  
Cell Therapy ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
High Blood Glucose ◽  
Pancreatic Progenitors ◽  
Treatment Of Diabetes ◽  
Cell Subpopulations ◽  
Glucose Responsiveness

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders. In order to replace the function of the destroyed pancreatic beta cells in diabetes, islet transplantation is the widely practiced treatment; however, it has several limitations. As an alternative approach, human pluripotent stem cells (hPSCs) can provide an unlimited source of pancreatic cells that have the ability to secrete insulin in response to high blood glucose level. However, determination of the appropriate pancreatic lineage candidate for the purpose of cell therapy for treatment of diabetes is still debated upon. While hPSC-derived beta cells are perceived as the ultimate candidate, the efficiency needs further improvement in order to obtain a sufficient number of glucose responsive β-cells for transplantation therapy. On the other hand, hPSC-derived pancreatic progenitors can be efficiently generated in vitro and can further mature into glucose responsive beta cells in vivo after transplantation. Herein, we discuss the advantages and predicted challenges associated with the use of each of the two pancreatic lineage products for diabetes cell therapy. Furthermore, we address co-generation of functionally relevant islet cell subpopulations and structural properties contributing to glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells.

scholarly journals Stem Cell Therapy for Diabetes: Beta Cells versus Pancreatic Progenitors

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 283 ◽  
Author(s):  
Bushra Memon ◽  
Essam M. Abdelalim
Keyword(s):  
Cell Therapy ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
High Blood Glucose ◽  
Pancreatic Progenitors ◽  
Treatment Of Diabetes ◽  
Cell Subpopulations ◽  
Glucose Responsiveness

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders. In order to replace the function of the destroyed pancreatic beta cells in diabetes, islet transplantation is the most widely practiced treatment. However, it has several limitations. As an alternative approach, human pluripotent stem cells (hPSCs) can provide an unlimited source of pancreatic cells that have the ability to secrete insulin in response to a high blood glucose level. However, the determination of the appropriate pancreatic lineage candidate for the purpose of cell therapy for the treatment of diabetes is still debated. While hPSC-derived beta cells are perceived as the ultimate candidate, their efficiency needs further improvement in order to obtain a sufficient number of glucose responsive beta cells for transplantation therapy. On the other hand, hPSC-derived pancreatic progenitors can be efficiently generated in vitro and can further mature into glucose responsive beta cells in vivo after transplantation. Herein, we discuss the advantages and predicted challenges associated with the use of each of the two pancreatic lineage products for diabetes cell therapy. Furthermore, we address the co-generation of functionally relevant islet cell subpopulations and structural properties contributing to the glucose responsiveness of beta cells, as well as the available encapsulation technology for these cells.

scholarly journals In vitro dissection of anti-diabetic effects of compound a, a dissociating glucocorticoid receptor ligand

2015 ◽  
Vol 67 (3) ◽  
pp. 941-947
Author(s):  
Milica Vujicic ◽  
Tamara Saksida ◽  
Ivana Nikolic ◽  
Ivana Stojanovic ◽  
Stanislava Stosic-Grujicic
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Immune Cell ◽  
Target Cells ◽  
Cytotoxic Action ◽  
Th17 Response ◽  
Compound A ◽  
Autoimmune Attack

Compound A (CpdA), or 2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethyl-ammonium chloride, is a stable analog of the hydroxyl phenyl aziridine precursor found in the Namibian shrub Salsola tuberculatiformis Botschantzev. It belongs to the group of so-called ?dissociated? GC receptor ligands that downmodulate pro-inflammatory gene expression via the transrepression mechanism, but without physically binding to DNA. We have recently reported that the in vivo administration of CpdA exerts a strong protective effect in a pharmacological model of type 1 diabetes in mice. The goal of this study was to investigate in more detail the effects of CpdA on multiple immune system components, as well as on target pancreatic beta cells in direct in vitro exposure. The utility of CpdA in diabetes prevention was evaluated through its addition to mitogen-activated spleen, lymph node and peritoneal cells of C57BL/6 mice, and to murine pancreatic islets and INS-1 and RINm5F beta cell lines. CpdA modulated immune cell-derived cytokine production in vitro by restraining the pro-inflammatory M1/Th1/Th17 response and switching it towards an anti-inflammatory Th2 profile. However, it did not preserve beta cells from the cytotoxic action of inflammatory cytokines. Thus, the anti-diabetic properties of CpdA are mediated through the modulation of immune cell differentiation pathways rather than through rescue of target cells from autoimmune attack.

scholarly journals In vivo and in vitro evaluation of the effects of Urtica dioica and swimming activity on diabetic factors and pancreatic beta cells

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Abbas Ranjbari ◽  
Mohammad Ali Azarbayjani ◽  
Ashril Yusof ◽  
Abdul Halim Mokhtar ◽  
Samad Akbarzadeh ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Urtica Dioica ◽  
Swimming Activity ◽  
In Vitro Evaluation

In vitro and in vivo insulinotropic actions of magainin-AM1 on pancreatic beta cells and high fat fed mice

2020 ◽  
Author(s):  
Falobi Ayodele Abiodun ◽  
Falana Ayokunle Benjamin ◽  
Yasser HA Abdel-Wahab ◽  
Peter R Flatt ◽  
Opeolu Ojo
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
High Fat
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