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Fetuin-A secretion from β-cells leads to accumulation of macrophages in islets, aggravates inflammation and impairs

Alpana Mukhuty1, Chandrani Fouzder1, Rakesh Kundu1

  • 1Cell Signaling Laboratory, Department of Zoology, Visva-Bharati University, Santiniketan 731 235, India.

Journal of Cell Science
|October 13, 2021
PubMed

Insights

Fetuin-A (AHSG) drives macrophage inflammation, contributing to islet dysfunction and impaired insulin secretion in type 2 diabetes. Reducing fetuin-A lessens these harmful effects.

Area of Science:

  • Endocrinology
  • Immunology
  • Metabolic Diseases

Background:

  • Obesity-mediated type 2 diabetes (T2D) involves elevated fetuin-A, chemokines, and islet macrophages.
  • Fetuin-A (AHSG) is implicated in T2D pathogenesis, but its precise role in islet inflammation requires elucidation.

Purpose of the Study:

  • To investigate the impact of MIN6 cell-derived fetuin-A on macrophage polarization.
  • To determine how M1 pro-inflammatory macrophages influence insulin secretion.
  • To explore fetuin-A's role in high-fat diet-induced diabetes.

Main Methods:

  • Assessed M1 macrophage marker expression (Emr1, Cd68, CD11c) and cytokine secretion.
  • Utilized MIN6 cells with and without fetuin-A suppression.
  • Employed Boyden chamber assays for macrophage chemotaxis.
  • Analyzed serum and islet tissues from high-fat fed mice.

Main Results:

  • Fetuin-A from MIN6 cells and islets increased M1 macrophage markers (∼1.8 fold) and cytokine secretion.
  • Fetuin-A suppression in MIN6 cells reduced M1 markers (∼1.5 fold).
  • High-fat feeding elevated serum/islet fetuin-A and cytokines, promoting islet macrophage infiltration and polarization.
  • M1 macrophages significantly reduced insulin secretion in MIN6 cultures (∼2.8 fold).

Conclusions:

  • Fetuin-A acts as a chemoattractant and macrophage polarizing factor, linking it to islet inflammation.
  • Fetuin-A contributes to beta-cell dysfunction and impaired insulin secretion in T2D.
  • Targeting fetuin-A may offer a therapeutic strategy for obesity-related T2D.
Keywords:
Fetuin-AHigh fat dietInsulin secretionIslet inflammationMacrophage polarizationPancreatic β-cell

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