Insulin Secretion, DNA Damage, and Apoptosis in Human and Rat Islets of Langerhans Following Exposure to Nitric Oxide, Peroxynitrite, and Cytokines

Hadjivassiliou, V.; Green, M.H.L.; James, R. F. L.; Swift, S. M.; Clayton, H. A.; Green, I.C.

doi:10.1006/niox.1998.0203

Cited by 73 publications

(66 citation statements)

References 63 publications

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“…DNA fragmentation could be detected early in islet cells after isolation and the beta-cells were primarily involved (Paraskevas et al, 2000). IL-1b and other cytokines have been demonstrated to be capable of inducing a decrease of insulin content and to induce DNA fragmentation of rat pancreatic islet beta-cells (Hadjivassiliou et al, 1998;Papaccio et al, 2002). The introduction of the potent immunosuppressive drugs tacrolimus (FK) and cyclosporine (CSA) has markedly improved the outcome of solid organ transplantation.…”

Section: Third Stage: Protein Crosslinking and Apoptotic Body Formationmentioning

confidence: 99%

Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

Hui

Dotta

Mario

et al. 2004

Journal Cellular Physiology

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The homeostatic control of beta-cell mass in normal and pathological conditions is based on the balance of proliferation, differentiation, and death of the insulinsecreting cells. A considerable body of evidence, accumulated during the last decade, has emphasized the significance of the disregulation of the mechnanisms regulating the apoptosis of beta-cells in the sequence of events that lead to the development of diabetes. The identification of agents capable of interfering with this process needs to be based on a better understanding of the beta-cell specific pathways that are activated during apoptosis. The aim of this article is fivefold: (1) a review of the evidence for beta-cell apoptosis in Type I diabetes, Type II diabetes, and islet transplantation, (2) to review the common stimuli and their mechanisms in pancreatic beta-cell apoptosis, (3) to review the role of caspases and their activation pathway in beta-cell apoptosis, (4) to review the caspase cascade and morphological cellular changes in apoptotic beta-cells, and (5) to highlight the putative strategies for preventing pancreatic beta-cells from apoptosis.

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Section: Third Stage: Protein Crosslinking and Apoptotic Body Formationmentioning

confidence: 99%

Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

Hui

Dotta

Mario

et al. 2004

Journal Cellular Physiology

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“…Islets were incubated in six-well plates at 37 C in a humidified atmosphere of 95% air/5% CO 2 for 48 h before treatment. Human islets were obtained from the Department of Surgery, University of Leicester, Leicester, UK and cultured in RPMI-1640 tissue culture medium containing 5·5 mmol/l glucose, 50 U/ml penicillin, 50 µg/ml streptomycin, 2 mmol/l -glutamine and 5% FCS (Hadjivassiliou et al 1998). Rat islets were cultured in RPMI-1640 containing 11 mmol/l glucose, 100 U/ml penicillin, 100 µg/ml streptomycin, 2 mmol/l -glutamine and 10% FCS.…”

Section: Rat and Human Islets Of Langerhansmentioning

confidence: 99%

“…In type 1 diabetes mellitus, where islet -cells are destroyed, there is evidence of increased cytokine production (Hussain et al 1996) and formation of peroxynitrite from reactive oxygen species and nitric oxide (Suarez-Pinzon et al 1997, Lakey et al 2001) -these can contribute to cell death by both apoptosis and necrosis (Eizirik et al 1996, Hadjivassiliou et al 1998, Hoorens et al 2001. For reviews on -cell death see Mauricio & Mandrup-Poulsen (1998) and Eizirik & Mandrup-Poulsen (2001).…”

Section: Introductionmentioning

confidence: 99%

“…Endogenous antioxidant enzymes, which protect against reactive oxygen species, were found to be lower in insulinproducing cells compared with other tissues (Grankvist et al 1981, Lenzen et al 1996, Tiedge et al 1997. It has been shown that overexpression of antioxidant enzymes (Lortz et al 2000) or the use of inhibitors of nitric oxide production (Hadjivassiliou et al 1998) protects insulin-producing cells against the harmful effects of certain cytokine or free radical combinations.…”

Section: Introductionmentioning

confidence: 99%

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Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its protein or mRNA expression in insulin-producing cells

Sigfrid¹,

Cunningham²,

Beeharry³

et al. 2003

Journal of Molecular Endocrinology

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Pancreatic -cells have low activities of the antioxidant enzyme catalase. Nitric oxide interacts with the haem group of catalase inhibiting its activity. We have studied the activity of catalase in -cells under conditions mimicking prediabetes and in which nitric oxide is generated from cytokine treatment in vitro. We also studied whether there is regulation of catalase enzyme activity by nitric oxide at the protein or gene expression level. RINm5F insulin-producing cells, treated for 24 h with cytokines, showed increased medium nitrite production (17±2·2 vs 0·3±0·2 pmol/µg protein) and significantly decreased cellular catalase activity (42·4±4·5%) compared with control cells. A similar reduction was seen in catalase-overexpressing RIN-CAT cells and in rat or human pancreatic islets of Langerhans. Catalase activity was also suppressed by the long-acting nitric oxide donor diethylenetriamine/nitric oxide adduct (Deta-NO) and this inhibition was reversible. The inhibition of catalase activity by cytokines in RINm5F cells was significantly reversed by the addition of the nitric oxide synthase 2 (NOS2) inhibitors nitro monomethylarginine or N-(3-(aminomethyl)benzyl)acetamidine (1400W). Protein expression was found to be unchanged in cytokine-or Deta-NO-treated RINm5F cells, while mRNA expression was marginally increased. We have shown that inhibition of catalase activity by cytokines is nitric oxide dependent and propose that this inhibition may confer increased susceptibility to cytokine-or nitric oxide-induced cell killing.

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“…During TLM preservation, pancreas ATP levels increase and RNA and protein are synthesized (14,15,43). Heat-shock protein levels increase (HSP 60, 70, and 32) (15), which may effect cell repair, neutralize free radicals, and inhibit apoptosis, resulting in higher yields of more viable islets (33,(44)(45)(46)(47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

Improved Islet Yields From Macaca Nemestrina and Marginal Human Pancreata After Two‐Layer Method Preservation and Endogenous Trypsin Inhibition

Matsumoto

Rigley

Reems

et al. 2003

American Journal of Transplantation

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We tested whether two-layer method (TLM) pancreas preservation and trypsin inhibition (Pefabloc) during processing allows longer preservation while retaining or improving viable islet recovery. Non-marginal primate (Macaca nemestrina) and marginal human (ischemic or preservation-injured) pancreata were processed with a research-oriented pan technique (Seattle method). Organs were processed upon arrival (∫ Pefabloc), or after TLM or University of Wisconsin solution (UW) preservation (π Pefabloc). Islet yield, viability, and function were assessed. Pefabloc increased M. nemestrina islet yields from 9696 ∫ 1749 IE/g to 15822∫ 1332 IE/g (p ∞ 0.01). Twolayer method preservation (∞ 6 h) further increased yields, to 23 769 ∫ 2773 IE/g (vs. π Pefabloc; p ∞0.01). Similarly, Pefabloc increased marginal human islet yields from 2473 ∫ 472 IE/g to 4723∫ 1006 IE/g (p ∞ 0.04). This increase was maintained after lengthy TLM preservation (Ͼ 30 h; 4801 ∫ 1066 IE/g). We also tested the applicability of TLM preservation (23.5 ∫ 3.2 h) to the processing of marginal human pancreata by the Edmonton/Immune Tolerance Network clinical protocol. Islet yield and function approached published results of pancreata processed 4.8 ∫ 0.8 h after organ recovery (p Ω 0.06). Pefabloc, and TLM vs. UW preservation, prolonged the tolerable interval between organ recovery and islet isolation. Islet yield, viability, and functionality improved from both marginal and nonmarginal pancreata.

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Insulin Secretion, DNA Damage, and Apoptosis in Human and Rat Islets of Langerhans Following Exposure to Nitric Oxide, Peroxynitrite, and Cytokines

Cited by 73 publications

References 63 publications

Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its protein or mRNA expression in insulin-producing cells

Improved Islet Yields From Macaca Nemestrina and Marginal Human Pancreata After Two‐Layer Method Preservation and Endogenous Trypsin Inhibition

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