2. Academic Validation
  3. Asprosin impairs insulin secretion in response to glucose and viability through TLR4/JNK-mediated inflammation

Asprosin impairs insulin secretion in response to glucose and viability through TLR4/JNK-mediated inflammation

  • Mol Cell Endocrinol. 2019 Apr 15;486:96-104. doi: 10.1016/j.mce.2019.03.001.
Taeseung Lee 1,  Subin Yun 2,  Ji Hoon Jeong 3,  Tae Woo Jung 4
Affiliations

Affiliations

  • 1 Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea.
  • 2 Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, USA.
  • 3 Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
  • 4 Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. Electronic address: [email protected].
PMID: 30853600 DOI: 10.1016/j.mce.2019.03.001
Abstract

Severe inflammation in the islets is observed in obese patients with type 2 diabetes. Inflammation in the islets is caused by obesity-induced serum free fatty acids. Asprosin is a fasting-induced adipokine, which contributes to hepatic glucose production. However, the effects of asprosin on inflammation and cellular dysfunction in pancreatic β-cells remain to be elucidated. Here, we demonstrated that treatment of mouse insulinoma MIN6 cells and human primary islets containing β-cells with palmitate increased asprosin expression and secretion. Treatment of MIN6 cells and human primary islets with palmitate increased phosphorylation of the inflammatory marker nuclear factor-kappa B (NFκB) and the release of pro-inflammatory cytokines including TNF and MCP-1 and decreased glucose-stimulated Insulin secretion and cell viability. However, siRNA-mediated suppression of asprosin reversed these changes. Recombinant asprosin treatment of MIN6 cells and human primary islets augmented the inflammation response, cellular dysfunction, and Apoptosis in a dose-dependent manner. Asprosin induced Toll-like Receptor (TLR) 4 expression and JNK phosphorylation. siRNA for TLR4 or JNK mitigated the effects of asprosin on inflammation and cellular dysfunction. These results suggest that palmitate-derived asprosin secretion from β-cells results in their inflammation and dysfunction through a TLR4/JNK-mediated pathway. This report suggests asprosin as a novel therapeutic target for the treatment of type 2 diabetes through preservation of β-cell function.

Keywords

Apoptosis; Asprosin; Inflammation; JNK; MIN6; TLR4; β-Cell.

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