Chemokine (C-X-C motif) ligand 14 (CXCL14) impairs pancreatic beta cell function
Other conference paper


全文

其它資訊
摘要Background and aims: Pancreatic beta cell dysfunction and insulin resistance are important factors in the pathophysiology of type 2 diabetes (T2D). Chemokines are chemo-attractants which guide the migration of inflammatory cells, especially macrophages, and have been shown to induce beta cell dysfunction. People with T2D or type 1 diabetes have higher serum levels of chemokines than normal individuals. The chemokine, CXCL12 (also known as SDF-1), and its receptor CXCR4, are crucial for beta cell differentiation, survival, and pancreatic islet genesis. However, these biological effects can be antagonized by CXCL14 which shares similar structure as CXCL12. Although CXCL14 knockout mice are protected from obesity-induced insulin resistance, whether CXCL14 may cause pancreatic beta cell dysfunction in the context of T2D has not been explored. Here, we aimed to examine the effects of CXCL14 on beta cell function.

Materials and methods: MIN6 cells, a pancreatic beta cell line derived from mouse insulinoma cells, and primary islets from C57/BL6 mice were treated with 100 ng/ml CXCL14 for different time points Expression of marker genes and total insulin production and glucose-stimulated insulin secretion (GSIS) were measured at different timepoints.

Results: In primary islets, CXCL14 impaired GSIS and total insulin production. CXCL14 treatment downregulated expression of genes related to insulin synthesis, including Pdx1, Isl1, Pax-6, MafA, Ins2, and genes involved in insulin secretion, including ZnT8, in both MIN6 cells and primary islets. In MIN6 cells, CXCL14 also reduced the expression of CXCL12 and CXCR4 and increased the phosphorylation of MAPK, ERK, and JNK in a time-dependent manner. CXCL14 activated MAPK which upregulated phosphorylation of ERK and JNK followed by activation of their downstream targets. CXCL14 also induced caspase 3 cleavage, suggesting a possible pro-apoptotic effect on beta cells.

Conclusion: CXCL14 impairs insulin synthesis and secretion and may be a potential target for treatment of T2D.
出版社接受日期19.08.2019
著者CAO Huanyi, TIAN Xiaoyu, CHUNG Chi Kong Arthur, MING Xing, LEE Heung Man, CHAN Chung Ngor Juliana, KONG Pik Shan
會議名稱East meets west symposium 2019
會議開始日28.09.2019
會議完結日29.09.2019
會議地點Hong Kong
會議國家/地區香港
出版年份2019
月份9
語言美式英語

上次更新時間 2020-14-05 於 17:01