03 Jun Pathway of Pancreatic Cell Death From Hyperglycemia Elucidated

MedicalResearch.com Interview with:
Dr. Soo Jung Park, Ph.D.
Senior Scientist
Division of Bioconvergence
Korea Basic Science Institute in Seoul, South Korea

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Diabetes is a leading cause of morbidity and mortality worldwide. The elevated level of blood glucose (hyperglycemia) can induce the cell death of the pancreatic beta cells which are responsible for the production of insulin. Loss of β-cell number and function underlies much of the pathology of diabetes. However, the mechanism is not fully understood, and we found the novel regulator for hyperglycemia induced beta cell death.
MedicalResearch.com: What should readers take away from your report?
Response: TSPAN2 protein levels dramatically increased in response to high glucose. High TSPAN2 levels upregulated phosphorylated-JNK (p-JNK) and induced apoptosis. p-JNK enhanced the phosphorylation of β-catenin (p-β-catenin) and Dickkopf-1 (Dkk1). Dkk1 knockdown by siRNA upregulated nuclear β-catenin, suggesting that it is a JNK/β-catenin-dependent pathway. siRNA-mediated TSPAN2 depletion in RNAKT-15 cells increased nuclear β-catenin. This decreased Bax activation, leading to marked protection against high glucose-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Thus, TSPAN2 might have induced Bax translocation and caspase-3 activation in pancreatic β cells, thereby promoting the apoptosis of RNAKT 15 cells by regulating the JNK/β-catenin pathway in response to high glucose concentrations.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study identified novel genes and novel pathways which are involved in diabetes, and they can be potentially useful to develop medicines for diabetes. If we can provide strategies for treating diabetes by targeting of TSPAN2 protein, they will inhibit the loss of pancreatic beta cells and relive the disease progression.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

FASEB J. 2016 May 31. pii: fj.201600240RR. [Epub ahead of print]
Tetraspanin-2 promotes glucotoxic apoptosis by regulating the JNK/β-catenin signaling pathway in human pancreatic β cells.
Hwang IH1, Park J2, Kim JM3, Kim SI4, Choi JS4, Lee KB4, Yun SH4, Lee MG1, Park SJ5, Jang IS6.

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Last Updated on June 3, 2016 by Marie Benz MD FAAD