Non-receptor tyrosine kinase inhibitors enhances β-cell survival by suppressing the PKCδ signal transduction pathway in streptozotocin - induced β-cell apoptosis

Udayakumar Karunakaran, Si Jun Park, Do Youn Jun, Taebo Sim, Keun Gyu Park, Myoung Ok Kim, In Kyu Lee

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 β-cell death in Type I and Type II diabetes. In this work we determined the effects of GNF-2, GNF-5 on pancreatic β-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 (PKCδ). 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 PKCδ. 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.

Original languageEnglish
Pages (from-to)1066-1074
Number of pages9
JournalCellular Signalling
Volume27
Issue number6
DOIs
Publication statusPublished - 2015 Jun 1

Fingerprint

Protein Kinase C-delta
Streptozocin
Protein-Tyrosine Kinases
Signal Transduction
Cell Survival
Caspase 3
Apoptosis
Mitogen-Activated Protein Kinase 10
Cell Death
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Type 2 Diabetes Mellitus
Blood Glucose
Insulin
Mutation
Proteins

Keywords

  • Signal transduction
  • Type 1 diabetes
  • Tyrosine kinase inhibitor
  • β-Cell failure

ASJC Scopus subject areas

  • Cell Biology

Cite this

Non-receptor tyrosine kinase inhibitors enhances β-cell survival by suppressing the PKCδ signal transduction pathway in streptozotocin - induced β-cell apoptosis. / Karunakaran, Udayakumar; Park, Si Jun; Jun, Do Youn; Sim, Taebo; Park, Keun Gyu; Kim, Myoung Ok; Lee, In Kyu.

In: Cellular Signalling, Vol. 27, No. 6, 01.06.2015, p. 1066-1074.

Research output: Contribution to journalArticle

Karunakaran, Udayakumar ; Park, Si Jun ; Jun, Do Youn ; Sim, Taebo ; Park, Keun Gyu ; Kim, Myoung Ok ; Lee, In Kyu. / Non-receptor tyrosine kinase inhibitors enhances β-cell survival by suppressing the PKCδ signal transduction pathway in streptozotocin - induced β-cell apoptosis. In: Cellular Signalling. 2015 ; Vol. 27, No. 6. pp. 1066-1074.
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