Academic Journal
The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes
| العنوان: | The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes |
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| المؤلفون: | Mabley, Jon G, Pacher, Pal, Murthy, Kanneganti G K, Williams, William, Southan, Garry J, Salzman, Andrew L, Szabo, Csaba |
| المصدر: | Journal of Endocrinology ; volume 198, issue 3, page 581-589 ; ISSN 0022-0795 1479-6805 |
| بيانات النشر: | Bioscientifica |
| سنة النشر: | 2008 |
| الوصف: | Endogenous purines including inosine have been shown to exert immunomodulatory and anti-inflammatory effects in a variety of disease models. The dosage of inosine required for protection is very high because of the rapid metabolism of inosine in vivo . The aim of this study was to determine whether a metabolic-resistant purine analogue, INO-2002, exerts anti-inflammatory effects in two animal models of type I diabetes. Type I diabetes was induced chemically with streptozotocin or genetically using the non-obese diabetic (NOD) female mouse model. Mice were treated with INO-2002 or inosine as required at 30, 100, or 200 mg/kg per day, while blood glucose and diabetes incidence were monitored. The effect of INO-2002 on the pancreatic cytokine profile was also determined. INO-2002 reduced both the hyperglycaemia and incidence of diabetes in both streptozotocin-induced and spontaneous diabetes in NOD mice. INO-2002 proved to be more effective in protecting against diabetes than the naturally occurring purine, inosine, when administered at the same dose. INO-2002 treatment decreased pancreatic levels of interleukin (IL)-12 and tumour necrosis factor-α, while increasing levels of IL-4 and IL-10. INO-2002 also reduced pancreatic levels of the chemokine MIP-1α. The inosine analogue, INO-2002, was protected more effectively than the naturally occurring purine, inosine, against development of diabetes in two separate animal models. INO-2002 exerts protective effects by changing the pancreatic cytokine expression from a destructive Th1 to a protective Th2 profile. The use of analogues of inosine such as INO-2002 should be considered as a potential preventative therapy in individuals susceptible to developing type I diabetes. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| DOI: | 10.1677/joe-07-0511 |
| الاتاحة: | http://dx.doi.org/10.1677/joe-07-0511 https://joe.bioscientifica.com/view/journals/joe/198/3/581.xml https://joe.bioscientifica.com/downloadpdf/journals/joe/198/3/581.xml |
| رقم الانضمام: | edsbas.77174980 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1677/joe-07-0511 |
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