Alloxan toxicity to the pancreatic B-cell

Malaisse, Willy

doi:10.1016/0006-2952(82)90571-8

Cited by 156 publications

(76 citation statements)

References 78 publications

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“…Several antioxidants which reduce HO · generating prevent alloxan diabetes. 1,2) The present results show that vitamin E and BHA prevent the decrease of intracellular ATP contents, the inhibition of insulin release, the collapse of Dy, and the DNA ladder formation in INS-1 cells treated with alloxan. These results suggest the possibility that lipid peroxidation may play a role in developing the cytotoxicity of INS-1 cells and the validity of the theory that lipid peroxidation is involved in alloxan-diabetes.…”

Section: Discussionsupporting

confidence: 49%

“…The destruction of pancreatic b-cells by alloxan is a major implication of the onset of diabetes mellitus which is a progressive event occurring over a 24-h period. 1,2) Further, it has been indicated that the diabetogenic concentration of alloxan in the body fluids is 5ϫ10 Ϫ4 M. 30) This points out the validity of an experimental condition using INS-1 cells treated with alloxan at a concentration below 0.5 mM over a 24 h period to elucidate alloxan diabetogenic action.…”

Section: Discussionmentioning

confidence: 99%

“…Since alloxan, which has the most potent diabetogenicity, selectively causes pancreatic b-cell death, 1,29) this compound has been used to induce experimental insulin-dependent diabetes mellitus, although the mechanism leading to cell death is not presently understood. We demonstrated that INS-1 cells treated with alloxan at a low concentration below 0.5 mM for 24 h resulted in a decrease in viability, intracellular ATP levels, and glucose-stimulated insulin release.…”

Section: Discussionmentioning

confidence: 99%

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Apoptosis and Mitochondrial Damage in INS-1 Cells Treated with Alloxan.

Sakurai

Katoh

Someno

et al. 2001

Biological & Pharmaceutical Bulletin

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A variety of mechanisms have been identified as responsible for the onset of diabetes mellitus. Alloxan shows a selective cytotoxicity on pancreatic b-cells and thus causes insulin-dependent (type I) diabetes mellitus. Although the mechanism of alloxan cytotoxicity is not yet clearly understood, several researchers 1,2) demonstrated that the diabetogenic action was initiated by the generation of reactive oxygen species (ROS). Alloxan is a mild oxidant and is easily reduced to alloxan radicals (A· Ϫ ) by GSH or ascorbic acid. 3) Our previous study 4) demonstrated that A· Ϫ can directly reduce O 2 and ferric ions to superoxide anion radical (O 2 · Ϫ ) and ferrous ions, respectively. The extreme and indiscriminate reactivity of ROS could easily explain the killing of b-cells by alloxan. In support of this hypothesis alloxan diabetes is prevented by HO · scavengers, 5-7) superoxide dismutase (SOD) 2) and vitamin E. 8) In addition, on the basis of in vivo and in vitro studies using rats and isolated islet cells, respectively, it was proposed that the process of alloxan toxicity involved the generation of HO · by which the DNA strands break of pancreatic islets is attacked to produce. 9-11) These findings indicate that DNA strand breaks are involved in the events of alloxan-diabetogenesis. However, the complex sequence of events that eventually leads to the DNA strand breaks and death of pancreatic b-cells in alloxan diabetes mellitus is not clear.Cell death might occur by one of two fundamental processes, necrosis or apoptosis. The biochemical hallmarks of apoptosis are the distribution of phosphatidylserine (PS) at the external surface of the plasma membrane (PS exposure) in the early stages, and the cleavage of chromosomal DNA into nucleosomal units, which appears to be the final blow in the cell death process. Recent studies have shown that different trigger such as IL-1b 12) and streptozotocin 13) can induce apoptosis in pancreatic b-cells. Although detailed studies indicate that alloxan can induce insulin-dependent diabetes mellitus, nothing is known about apoptotic action or the sequence of cellular events of alloxan on the b-cells.According to current understanding, mitochondrial damage seems to occur in the early phase of apoptosis and to participate in the control of apoptosis. 14,15) Release of cytochrome c and apoptosis induced factor from mitochondria into cytoplasm during mitochondrial permeability transition cause to active caspase family, leading to the completion of apoptosis. 15,16) Isolated liver mitochondria incubated with alloxan alters respiration, decreases in the concentration of adenine nucleotides, causes Ca 2ϩ release, and changes in the Dy, 17,18) indicating that alloxan directly induces the mitochondrial damage. However, the relationship between diabetes, apoptosis and mitochondrial damage has remained elusive.INS-1 cells were established by X-ray-induced rat transplantable insulinoma, and have retained the similar ability of glucose-stimulated insulin release of native b-cells. 19) INS-1 ...

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Apoptosis and Mitochondrial Damage in INS-1 Cells Treated with Alloxan.

Sakurai

Katoh

Someno

et al. 2001

Biological & Pharmaceutical Bulletin

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“…Furthermore, only the glucose-responsive cells were found to benefit from the protective effect of the sugar against alloxan-induced damage [59]. These results can be explained by the opposite effects of glucose and alloxan upon the cellular redox state and, hence, upon cell survival [59,60]. Besides its ability to prevent a drop in cellular NAD(P)H following alloxan exposure, glucose is also capable of counteracting the cell-destructive consequences of a cytotoxic interaction with the B cells (Fig.…”

Section: Coexistence Of Functionally Diverse B-cell Subpopulationsmentioning

confidence: 99%

The biosociology of pancreatic B cells

1987

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“…Since the initial report of Sen & Bhattachaya (1952), it is well established that glucose prevents the development of alloxan-induced β-cell damage in vivo (Scheynius & Taljedal, 1971;Jansson & Sandler, 1988) and in vitro (Malaisse, 1982). This protection of glucose against alloxan-induced β-cell damage is mediated through the metabolism of glucose within the pancreatic β-cells.…”

Section: Introductionmentioning

confidence: 99%