| First Author | Lee T | Year | 2019 |
| Journal | Mol Cell Endocrinol | Volume | 486 |
| Pages | 96-104 | PubMed ID | 30853600 |
| Mgi Jnum | J:275326 | Mgi Id | MGI:6303505 |
| Doi | 10.1016/j.mce.2019.03.001 | Citation | Lee T, et al. (2019) Asprosin impairs insulin secretion in response to glucose and viability through TLR4/JNK-mediated inflammation. Mol Cell Endocrinol 486:96-104 |
| abstractText | 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 beta-cells remain to be elucidated. Here, we demonstrated that treatment of mouse insulinoma MIN6 cells and human primary islets containing beta-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 (NFkappaB) 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 beta-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 beta-cell function. |
