Apolipoprotein A-IV and its derived peptide, T55−121, improve glycemic control and increase energy expenditure  

作　　者：Zhen Cao Lei Lei Ziyun Zhou Shimeng Xu Linlin Wang Weikang Gong Qi Zhang Bin Pan Gaoxin Zhang Quan Yuan Liujuan Cui Min Zheng Tao Xu You Wang Shuyan Zhang Pingsheng Liu 

机构地区：[1]National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]The State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China [4]Luxembourg Centre for Systems Biomedicine,University of Luxembourg,Esch-sur-Alzette 4362,Luxembourg [5]Guangzhou Regenerative Medicine and Health Guangdong Laboratory(Bioland Laboratory),Guangzhou,Guangdong 510005,China [6]Department of Computer Science,School of Computing,National University of Singapore,Singapore 117417,Singapore [7]School of Basic Medical Sciences,Southwest Medical University,Luzhou,Sichuan 646000,China [8]The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,National Clinical Research Center for Infectious Diseases,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou,Zhejiang 310003,China [9]Beijing Key Laboratory of Emerging Infectious Diseases,Institute of Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China [10]Beijing Institute of Infectious Diseases,Beijing 100015,China [11]National Center for Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China [12]National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases,Beijing 100015,China

出　　处：《Life Metabolism》2024年第4期1-12,共12页生命代谢（英文）

基　　金：supported by the National Natural Science Foundation of China(92357302,32170787,and 32100557);the National Key Research and Development Program of China(2018YFA0800700,2023YFA1801103,and 2018YFA0800900);Researches on human islets were supported by the National Natural Science Foundation of Tianjin Municipal Human Resources and Social Security Bureau(XB202011).

摘　　要：It is crucial to understand the glucose control within our bodies.Bariatric/metabolic surgeries,including laparoscopic sleeve gastrec-tomy(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 gly-cemic 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 pancreaticβcells,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.

关 键 词：bariatric/metabolic surgeries PROTEOMICS apolipoprotein A-IV glucose tolerance glucose-stimulated insulin secretion human islets 

分 类 号：R58[医药卫生—内分泌]