Chen Younan, Carlessi Rodrigo, Walz Nikita, Cruzat Vinicius Fernandes, Keane Kevin, John Abraham N, Jiang Fang-Xu, Carnagarin Revathy, Dass Crispin R, Newsholme Philip
School of Biomedical Sciences, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia; Key Laboratory of Transplant Engineering and Immunology, NHFPC; Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, PR China.
School of Biomedical Sciences, CHIRI Biosciences, Curtin University, GPO Box U1987, Perth, Western Australia, Australia.
Mol Cell Endocrinol. 2016 May 5;426:50-60. doi: 10.1016/j.mce.2016.02.004. Epub 2016 Feb 8.
Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein, associated with lipid catabolism and insulin resistance. In the present study, PEDF increased chronic and acute insulin secretion in a clonal rat β-cell line BRIN-BD11, without alteration of glucose consumption. PEDF also stimulated insulin secretion from primary mouse islets. Seahorse flux analysis demonstrated that PEDF did not change mitochondrial respiration and glycolytic function. The cytosolic presence of the putative PEDF receptor - adipose triglyceride lipase (ATGL) - was identified, and ATGL associated stimulation of glycerol release was robustly enhanced by PEDF, while intracellular ATP levels increased. Addition of palmitate or ex vivo stimulation with inflammatory mediators induced β-cell dysfunction, effects not altered by the addition of PEDF. In conclusion, PEDF increased insulin secretion in BRIN-BD11 and islet cells, but had no impact on glucose metabolism. Thus elevated lipolysis and enhanced fatty acid availability may impact insulin secretion following PEDF receptor (ATGL) stimulation.
色素上皮衍生因子（PEDF）是一种多功能糖蛋白，与脂质分解代谢和胰岛素抵抗相关。在本研究中，PEDF增加了克隆大鼠β细胞系BRIN-BD11中的慢性和急性胰岛素分泌，而不改变葡萄糖消耗。PEDF还刺激了原代小鼠胰岛的胰岛素分泌。海马通量分析表明，PEDF不会改变线粒体呼吸和糖酵解功能。已鉴定出假定的PEDF受体——脂肪甘油三酯脂肪酶（ATGL）——的胞质存在，并且PEDF强烈增强了ATGL相关的甘油释放刺激，同时细胞内ATP水平增加。添加棕榈酸酯或用炎症介质进行体外刺激会诱导β细胞功能障碍，添加PEDF不会改变这些作用。总之，PEDF增加了BRIN-BD11和胰岛细胞中的胰岛素分泌，但对葡萄糖代谢没有影响。因此，脂解作用增强和脂肪酸可用性增加可能会在PEDF受体（ATGL）刺激后影响胰岛素分泌。
