[期刊论文]


Fetuin-A secretion from β-cell accumulates macrophages in islets, aggravates inflammation and impairs insulin secretion

作   者:
Alpana Mukhuty;Chandrani Fouzder;Rakesh Kundu;

出版年:暂无

页    码:暂无
出版社:The Company of Biologists


摘   要:

Elevated fetuin-A levels, chemokines and islet resident macrophages are crucial factors associated with obesity mediated Type 2 Diabetes (T2D). Here, the aim of the study was to investigate the effect of MIN6 (mouse insulinoma cell line) derived fetuin-A in macrophage polarization and decipher the effect of M1 type pro-inflammatory macrophages in commanding over insulin secretion. MIN6 and islet derived fetuin-A induced expression of M1 type macrophage markers, Emr1, Cd68 and CD11c (∼1.8 fold) along with increased cytokine secretion. Interestingly, suppression of fetuin-A in MIN6 successfully reduced M1 markers by ∼1.5 fold. MIN6 derived fetuin-A also induced chemotaxis of macrophages in Boyden chamber chemotaxis assay. Further, high fat feeding in mice showed elevated cytokine and fetuin-A content in serum and islets, and also migration and polarization of macrophages to the islets while β-cells failed to cope up with increased insulin demand. Moreover, in MIN6 culture, M1 macrophages sharply decreased insulin secretion by ∼2.8 fold. Altogether our results support an association of fetuin-A with islet inflammation and β-cell dysfunction, owing to its role as a key chemoattractant and macrophage polarizing factor.



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所属期刊
Journal of Cell Science
ISSN: 0021-9533
来自:The Company of Biologists