Protection of B cells against the effect of alloxan

Abdel‐Rahman, Mohamed S.; Elrakhawy, Fatma I.; Iskander, Fakhry A.

doi:10.1016/0378-4274(92)90007-7

Cited by 14 publications

(3 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is notoriously difficult to reliably detect and quantify apoptosis in beta cells in situ due to the short duration of the process and rapid elimination of apoptotic cells, especially in alloxan-treated mice where only a small beta cell number remains. Besides apoptosis as a mechanism of alloxan-induced beta cell death, numerous researchers reported that alloxan mainly induces beta cell loss by necrosis [ 29 – 32 ].…”

Section: Discussionmentioning

confidence: 99%

Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin

et al. 2015

View full text Add to dashboard Cite

One week of treatment with EGF and gastrin (EGF/G) was shown to restore normoglycemia and to induce islet regeneration in mice treated with the diabetogenic agent alloxan. The mechanisms underlying this regeneration are not fully understood. We performed genetic lineage tracing experiments to evaluate the contribution of beta cell neogenesis in this model. One day after alloxan administration, mice received EGF/G treatment for one week. The treatment could not prevent the initial alloxan-induced beta cell mass destruction, however it did reverse glycemia to control levels within one day, suggesting improved peripheral glucose uptake. In vitro experiments with C2C12 cell line showed that EGF could stimulate glucose uptake with an efficacy comparable to that of insulin. Subsequently, EGF/G treatment stimulated a 3-fold increase in beta cell mass, which was partially driven by neogenesis and beta cell proliferation as assessed by beta cell lineage tracing and BrdU-labeling experiments, respectively. Acinar cell lineage tracing failed to show an important contribution of acinar cells to the newly formed beta cells. No appearance of transitional cells co-expressing insulin and glucagon, a hallmark for alpha-to-beta cell conversion, was found, suggesting that alpha cells did not significantly contribute to the regeneration. An important fraction of the beta cells significantly lost insulin positivity after alloxan administration, which was restored to normal after one week of EGF/G treatment. Alloxan-only mice showed more pronounced beta cell neogenesis and proliferation, even though beta cell mass remained significantly depleted, suggesting ongoing beta cell death in that group. After one week, macrophage infiltration was significantly reduced in EGF/G-treated group compared to the alloxan-only group. Our results suggest that EGF/G-induced beta cell regeneration in alloxan-diabetic mice is driven by beta cell neogenesis, proliferation and recovery of insulin. The glucose-lowering effect of the treatment might play an important role in the regeneration process.

show abstract

Section: Discussionmentioning

confidence: 99%

Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In vivo, over-expression of Cu/ZnSOD in diabetic animals provides protection against the development of alloxan-or STZ-induced diabetes. Moreover, addition of scavenging agents such as SOD, Catalase (Cat), guanidinoethyldisulphide, and metal chelators prior to alloxan, STZ, or cytokine exposure has prevented b cell death in isolated islets (Gandy et al 1982, Abdel-Rahman et al 1992, Suarez-Pinzon et al 2001. Lower concentrations of H 2 O 2 , however, seem to be involved in the regulation of physiological processes, e.g.…”

Section: Introductionmentioning

confidence: 99%

Peroxiredoxin III protects pancreatic β cells from apoptosis

Wolf

Aumann²,

Michalska³

et al. 2010

Journal of Endocrinology

View full text Add to dashboard Cite

Type 1 diabetes mellitus is characterized by a progressive autoimmune destruction of insulin-producing b cells. Macrophages and T lymphocytes release cytokines, which induce the synthesis of oxygen and nitrogen radicals in the pancreatic islets. The resulting cellular and mitochondrial damage promotes b cell death. b cells are very sensitive to the autoimmune free radical-dependent attack due to their low content of antioxidant enzymes such as glutathione peroxidase and catalase. A focal point of b cell protection should be the control of the mitochondrial redox status, which will result in the preservation of metabolic stimulus-secretion coupling. For this reason, there is a considerable interest in the mitochondrial peroxiredoxin III (PRX III), a thioredoxindependent peroxide reductase, which was shown to be able to protect against both oxidative and nitrosative stress.Using the Tet-On-system, we generated stably transfected rat insulinoma cells over-or under-expressing PRX III in a doxycyclin-dependent manner to analyze the effect of increased or decreased amounts of cellular PRX III, following treatment with several stressors. We provide evidence that PRX III protects pancreatic b cells from cell stress induced by accumulation of hydrogen peroxide, or the induction of inducible nitric oxide synthase or caspase-9 and -3 by pro-inflammatory cytokines or streptozotocin. Basal insulin secretion was markedly decreased in cells expressing lower levels of PRX III. We suggest PRX III may be a suitable target for promoting deceleration or even prevention of stress-associated apoptosis in pancreatic b cells and the manifestation of insulin-dependent diabetes mellitus.

show abstract

“…Although the precise diabetogenic mechanism of alloxan is not fully understood, there is some evidence indicating that the tissue damage induced by alloxan is mediated through the formation of reactive oxygen species (ROS, Heikkila et al, 1976;Cohen and Heikkila, 1974;Kim et al, 1994;Park et al, 1995). There are many reports that the scavengers of ROS can ameliorate alloxan toxicity in vitro (Gandy et al, 1982;Abdel-Rahman et al, 1992) and in vivo (Grakvist et al, 1981;Heikkila and Cabbat, 1982). Okamoto (1985) proposed that the primary target of ROS produced from alloxan is the DNA of pancreatic β-cells.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of Amomi semen extract on alloxan‐induced pancreatic β‐cell damage

Lee

Park

Kim

et al. 2007

Phytotherapy Research

View full text Add to dashboard Cite

The protective effect of Amomi semen extract (ASE) on alloxan-induced pancreatic β β β β β-cell damage was investigated in HIT T-15 cells, a Syrian hamster pancreatic β β β β β-cell line. Alloxan caused pancreatic β β β β β-cell damage through the generation of reactive oxygen species (ROS), the elevation of cytosolic free Ca 2+ + + + + , DNA fragmentation and the decrease of cellular NAD + + + + + and ATP levels. All these effects of alloxan were significantly prevented by pretreatment with a water-soluble extract of Amomi semen. Pretreatment with ASE in pancreatic islets isolated from mice, also significantly abolished the inhibition of glucose-stimulated insulin secretion by alloxan. The results of this study provide evidence that ASE may have a protective activity on alloxaninduced β β β β β-cell damage, and that the protective effect is primarily due to the inhibition of ROS generation by alloxan.

show abstract

Protection of B cells against the effect of alloxan

Cited by 14 publications

References 17 publications

Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin

Beta Cell Mass Restoration in Alloxan-Diabetic Mice Treated with EGF and Gastrin

Peroxiredoxin III protects pancreatic β cells from apoptosis

Protective effect of Amomi semen extract on alloxan‐induced pancreatic β‐cell damage

Contact Info

Product

Resources

About