Original Article
Effect of Janus kinase 2 depletion on pancreatic β cell survival and function
Xiaoyu He, Fei Xiong, Wagner Kay-Uwe, Congyi Wang
Published 2017-10-27
Cite as Chin J Diabetes Mellitus, 2017, 09(10): 612-616. DOI: 10.3760/cma.j.issn.1674-5809.2017.10.004
Abstract
ObjectiveTo explore the effects of Janus kinase 2 (Jak2) depletion on pancreatic β cell survival and function.
MethodsRip-CreER-Jak2f/f male mice hybridized by Rip-CreER mice and Jak2f/f mice (8 weeks old and 20-22 grams weight) were induced by tamoxifen to generate β cell-specific Jak2 knockout (KO) mice (KO group, n=40). Jak2f/f male mice induced by tamoxifen were as control group (n=40). Jak2 gene depleted at day 7 after tamoxifen-induction and confirmed by Polymerase chain reaction (PCR) and western blotting analyses. β cell function were evaluated by random glucose levels and intraperitoneal glucose tolerance test (IPGTT). The pathogenic, sub-pathogenic and lethal doses of streptozocin (STZ) were administrated respectively to observe the effects of Jak2 on β cell survival. Comparison of the two treatments were analyzed using the student's t-test, the incidence of diabetes and the mortality of mice were analyzed by Kaplan-Meier survival model.
ResultsInducible pancreatic β cell-specific Jak2 knockout mouse model were established successfully. None of the KO mice developed diabetes spontaneously. There were no significant differences in the incidence of diabetes between KO and control mice either stimulated with pathogenic or sub-pathogenic doses of STZ (83.3% vs 91.6%, P=0.392 8; 20% vs 20%, P>0.05; respectively); No significant differences were found in the average glucose levels between KO and control mice [(11.0±6.6) vs (12.0±5.7) mmol/L, P=0.425 8]. There were no significant differences in the motility rate between KO and control mice when stimulated with lethal dose of STZ (92.3% vs 93.75%, P=0.554 0).
ConclusionJak2 gene is highly expressed in pancreatic β cell, however, Jak2 has no effects on β cell survival and function.
Key words:
Janus kinase 2 gene; βcell; Oxidative stress; Islet function
Contributor Information
Xiaoyu He
The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Fei Xiong
Wagner Kay-Uwe
Congyi Wang