| First Author | Wang Q | Year | 2023 |
| Journal | Mol Cell Endocrinol | Volume | 576 |
| Pages | 112043 | PubMed ID | 37574124 |
| Mgi Jnum | J:344663 | Mgi Id | MGI:7523804 |
| Doi | 10.1016/j.mce.2023.112043 | Citation | Wang Q, et al. (2023) SAA1 exacerbates pancreatic beta-cell dysfunction through activation of NF-kappaB signaling in high-fat diet-induced type 2 diabetes mice. Mol Cell Endocrinol 576:112043 |
| abstractText | Insufficient decompensated insulin secretion and insulin resistance caused by pancreatic beta-cell dysfunction are the pathological bases of type 2 diabetes mellitus (T2DM). Glucolipotoxicity in pancreatic beta-cells is an important factor leading to their dysfunction, closely related to inflammatory signals, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress (ERs). However, there may be other unproven regulatory mechanisms that govern pancreatic beta-cell dysfunction. Therefore, further elucidation of the underlying mechanisms that lead to pancreatic beta-cells dysfunction will provide a sufficient theoretical basis for the more effective prevention and treatment of T2DM. As a stress protein with pro-inflammatory properties, Serum Amyloid 1 (SAA1) promotes the progression of metabolic syndrome-related diseases by activating immune cells and damaging endothelial cells. In the development of T2DM, the activation of nuclear factor-kappa B (NF-kappaB) signaling aggravates pancreatic beta-cells dysfunction under the stimulation of free fatty acids (FFAs), inflammatory factors, and chemokines. Moreover, the facilitating effect of SAA1 on the activation of the NF-kappaB signaling pathway has been demonstrated in other studies. In the present study, we demonstrated that SAA1 inhibits insulin secretion and promotes apoptotic molecular expression in pancreatic cells and islets and that NF-kappaB signaling inhibitors could reduce this effect of SAA1. SAA1 deficiency improved high-fat diet (HFD)-induced pancreatic beta-cell dysfunction and decreased expression of NF-kappaB signaling molecules. Our findings suggested that HFD-induced SAA1 might exacerbate T2DM by enhancing pancreatic beta-cell dysfunction; such a function of SAA1 might depend on NF-kappaB signaling activation. |
