CMV-hFasL transgenic mice are sensitive to low doses of streptozotocin-induced type I diabetes mellitus
Abstract
AIM: To investigate the role of Fas-FasL pathway in the pathogenesis of streptozotocin (STZ)-induced type I diabetes mellitus.
METHODS: Low dose injections of STZ were used to induce type I diabetes mellitus in the CMV-hFasL transgenic mice. Blood glucose concentration was measured with Glucotrand Plus blood glucose test strips. Expression of hFasL was detected by RT-PCR and Western blotting. The severity of insulitis was determined by histological examination. Expressions of IL-1beta and TNF-alpha mRNA in the pancreas were detected by semi-quantitative RT-PCR analysis. Fas expression in apoptotic RIN-5F cells was also confirmed by RT-PCR in vitro.
RESULTS: hFasL was expressed in the islets of CMV-hFasL transgenic mice. The transgenic mice were sensitive to diabetic induction than the control WT mice. IL-1beta and TNF-alpha expressions in the pancreas of CMV-hFasL transgenic mice were far more than that in WT mice. We also found STZ and IL-1beta could both induce higher expression of Fas in RIN-5F. The combining of Fas-FasL could lead to the apoptosis of beta cells in the CMV-hFasL transgenic mice.
CONCLUSION: Fas-FasL interaction plays a significant role in the pathogenic mechanism of type I diabetes mellitus.
Keywords:
METHODS: Low dose injections of STZ were used to induce type I diabetes mellitus in the CMV-hFasL transgenic mice. Blood glucose concentration was measured with Glucotrand Plus blood glucose test strips. Expression of hFasL was detected by RT-PCR and Western blotting. The severity of insulitis was determined by histological examination. Expressions of IL-1beta and TNF-alpha mRNA in the pancreas were detected by semi-quantitative RT-PCR analysis. Fas expression in apoptotic RIN-5F cells was also confirmed by RT-PCR in vitro.
RESULTS: hFasL was expressed in the islets of CMV-hFasL transgenic mice. The transgenic mice were sensitive to diabetic induction than the control WT mice. IL-1beta and TNF-alpha expressions in the pancreas of CMV-hFasL transgenic mice were far more than that in WT mice. We also found STZ and IL-1beta could both induce higher expression of Fas in RIN-5F. The combining of Fas-FasL could lead to the apoptosis of beta cells in the CMV-hFasL transgenic mice.
CONCLUSION: Fas-FasL interaction plays a significant role in the pathogenic mechanism of type I diabetes mellitus.