Cao Zhen, Lei Lei, Zhou Ziyun, Xu Shimeng, Wang Linlin, Gong Weikang, Zhang Qi, Pan Bin, Zhang Gaoxin, Yuan Quan, Cui Liujuan, Zheng Min, Xu Tao, Wang You, Zhang Shuyan, Liu Pingsheng
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Life Metab. 2024 Mar 14;3(4):loae010. doi: 10.1093/lifemeta/loae010. eCollection 2024 Aug.
It is crucial to understand the glucose control within our bodies. Bariatric/metabolic surgeries, including laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB), provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes (T2D). For the first time, a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics. Apolipoprotein A-IV (apoA-IV) was revealed to be increased dramatically in diabetic obese patients following LSG, and a similar effect was observed in patients after RYGB surgery. Moreover, recombinant apoA-IV protein treatment was proven to enhance insulin secretion in isolated human islets. These results showed that apoA-IV may play a crucial role in glycemic control in humans, potentially through enhancing insulin secretion in human islets. ApoA-IV was further shown to enhance energy expenditure and improve glucose tolerance in diabetic rodents, through stimulating glucose-dependent insulin secretion in pancreatic β cells, partially via Gαs-coupled GPCR/cAMP (G protein-coupled receptor/cyclic adenosine monophosphate) signaling. Furthermore, T55-121, truncated peptide 55-121 of apoA-IV, was discovered to mediate the function of apoA-IV. These collective findings contribute to our understanding of the relationship between apoA-IV and glycemic control, highlighting its potential as a biomarker or therapeutic target in managing and improving glucose regulation.
了解我们体内的血糖控制至关重要。减重/代谢手术，包括腹腔镜袖状胃切除术（LSG）和Roux-en-Y胃旁路术（RYGB），为探索维持葡萄糖稳态的潜在关键因素提供了一条途径，因为这些手术在改善重度2型糖尿病（T2D）患者的血糖控制方面已显示出有前景的结果。首次通过蛋白质组学发现并分析了LSG术后患者血清蛋白群体的显著变化。载脂蛋白A-IV（apoA-IV）在LSG术后的糖尿病肥胖患者中显著增加，RYGB手术患者也观察到类似效果。此外，重组apoA-IV蛋白治疗被证明可增强分离的人胰岛中的胰岛素分泌。这些结果表明，apoA-IV可能在人类血糖控制中起关键作用，可能是通过增强人胰岛中的胰岛素分泌。进一步研究表明，apoA-IV通过刺激胰腺β细胞中葡萄糖依赖性胰岛素分泌，部分通过Gαs偶联的GPCR/cAMP（G蛋白偶联受体/环磷酸腺苷）信号传导，增强糖尿病啮齿动物的能量消耗并改善葡萄糖耐量。此外，发现apoA-IV的截短肽55-121（T55-121）可介导apoA-IV的功能。这些共同发现有助于我们理解apoA-IV与血糖控制之间的关系，突出了其作为管理和改善血糖调节的生物标志物或治疗靶点的潜力。
