Species differences in susceptibility of transplanted and cultured pancreatic islets to the beta-cell toxin alloxan.
ABSTRACT The beta-cell toxin alloxan, which produces oxygen radicals, is a model substance in studies of type 1 diabetes. Recently, human beta-cells have been found to be relatively resistant to this toxin. To clarify species differences in alloxan diabetogenicity, and oxygen radical toxicity, mouse, rat, rabbit, dog, pig, human and guinea pig islets have been studied after alloxan exposure. Using a standardized in vivo model, where islets were transplanted to nude mice, the different islets were compared. The results demonstrated that mouse and rat islet grafts were morphologically disturbed by alloxan and ROS. Rabbit and dog islet graft morphology was reasonably intact; and human, porcine, and guinea pig islet grafts were all well preserved. Furthermore, ultrastructural signs of apoptosis and necrosis, disturbances in the insulin secretory pattern during and after an alloxan perifusion, and islet lysosomal enzyme activities were studied in vitro in islets from some species. Guinea pig beta-cells were affected by alloxan, but a regeneration process compensated for the observed apoptotic and necrotic cell death. Human islets did not show any signs of alloxan-induced damage in the different models studied. Finally, no correlation between high alloxan sensitivity and high lysosomal enzyme activity was found. Thus, the beta-cell lysosomes are hardly specific targets for alloxan.
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ABSTRACT: Streptozotocin (STZ) and alloxan (ALX), widely used to induce diabetes in experimental animals, have different structures and mechanisms of action. We investigated those effects of these drugs on the immune system that might influence engraftment efficiency and graft survival in transplantation models, and their cytotoxicity on hematopoietic cell lines.Immunology Letters 01/2015; 208(2). DOI:10.1016/j.imlet.2014.12.006 · 2.37 Impact Factor
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ABSTRACT: Islet transplantation is an attractive treatment of type 1 diabetes mellitus (T1DM). Animal models of diabetes mellitus (DM) contribute a lot to the experimental studies of islet transplantation and to evaluations of isolated islet grafts for future clinical applications. Diabetic nonhuman primates (NHPs) represent the suitable models of DMs to better evaluate the effectiveness of islet transplantation, to assess new strategies for controlling blood glucose (BG), relieving immune rejection, or prolonging islet survival, and eventually to translate the preclinical data into tangible clinical practice. This review introduces some NHP models of DM, clarifies why and how the models should be used, and elucidates the usefulness and limitations of the models in islet transplantation.Journal of Diabetes Research 01/2014; 2014:785948. DOI:10.1155/2014/785948 · 3.54 Impact Factor
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ABSTRACT: Background: Gold nanoparticles (AuNPs) have a wide range of applications in various fields. This study provides an understanding of the modulatory effects of AuNPs on an antioxidant system in male Wistar diabetic rats with autism spectrum disorder (ASD). Normal littermates fed by control mothers were injected with citrate buffer alone and served as normal, untreated controls controlin this study. Diabetes mellitus (DM) was induced by administering a single intraperitoneal injection of streptozotocin (STZ) (100 mg/kg) to the pups of (ND) diabetic group, which had been fasted overnight. Autistic pups from mothers that had received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception were randomly divided into 2 groups (n 2 7/group) as follow; administering single intraperitoneal injection of streptozotocin (STZ) ( (100 mg/kg) to the overnight fasted autistic pups of (AD) autistic diabetic group. The treatment was started on the 5th day after STZ injection with the same dose as in group II and it was considered as 1st day of treatment with gold nanoparticles for 7 days to each rat of (group IV) treated autistic diabetic group(TAD) at a dosage of 2.5 mg/kg. b. wt. Results: At this dose of administration AuNPs, the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were greater in group TAD compared with the control group (P < 0.05). Oxidised glutathione levels were lower (P > 0.05) in the liver of autistic diabetic AuNPs -supplemented rats, whereas reduced glutathione was markedly higher than in control rats, especially after administration of AuNPs. Moreover, the kidney functions in addition to the fat profile scoring supported the protective potential of that dose of AuNPs. The beta cells revealed euchromatic nuclei with no evidence of separation of nuclear membrane. Conclusions: Our results showed that AuNPs improved many of the oxidative stress parameters (SOD, GPx and, CAT), plasma antioxidant capacity (ORAC) and lipid profile relative to the other parameters. In addition to the apparent reversibility of the pancreatic B cell in group IV which may reflect the regenerative capacity of AuNPs. © 2015 S. Karger AG, Basel.Cellular Physiology and Biochemistry 01/2015; 35(2):586-600. DOI:10.1159/000369721 · 3.55 Impact Factor