Journal
CELLULAR SIGNALLING
Volume 27, Issue 6, Pages 1066-1074Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2015.01.018
Keywords
beta-Cell failure; Type 1 diabetes; Tyrosine kinase inhibitor; Signal transduction
Categories
Funding
- National Research Foundation of Korea (NRF) - Korean Ministry of Education (MOE) [2012R1A2A1A03670452]
- Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A111345]
- National Research Foundation of Korea [2012R1A2A1A03670452] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
GNF-2 and GNF-5 are members of a new class of non-receptor tyrosine kinases inhibitors that possess excellent selectivity towards imatinib-resistant mutations found in chronic myeloid leukemia patients. On the other hand recent reports implicate abnormal tyrosine kinase signaling in beta-cell death in Type I and Type II diabetes. In this work we determined the effects of GNF-2, GNF-5 on pancreatic beta-cell death caused by streptozotocin (STZ). STZ treatment causes apoptosis of INS-1 cells by activation of intracellular ROS, c-jun N-terminal kinase (JNK), caspase 3, and caspase 3-dependent activation of protein kinase C delta (PKC delta). GNF-2 and GNF-5 increased cell viability and attenuated STZ-induced intracellular ROS and significantly reduced the activation of JNK, caspase 3, and caspase 3-dependent activation of PKC delta. In studies with intact mice, GFN-2 and GNF-5 prevented the loss of beta cells and the increase in blood glucose produced by STZ-treated control mice. Furthermore, immunohistochemical analysis revealed that GNF-2 and GNF-5 increased insulin protein levels in STZ-treated mice when compared with control mice. These findings suggest that non-receptor tyrosine kinase inhibitors provide a new approach for the treatment of new-onset Type land Type II diabetes. (C) 2015 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available