机构：[1]Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.[2]Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[3]Sichuan University West China Hospital, Department of Experimental Animal Center, West China Hospital of Sichuan University, Chengdu 610041, China.四川大学华西医院[4]Division of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[5]Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.四川省人民医院
Glucose is essential to the physiological processes of vertebrates. Mammalian physiological stability requires a relatively stable blood glucose level (~5 mmol/L), whereas other vertebrates have greater flexibility in regulating blood glucose (0.5-25 mmol/L). GCGR family receptors play an important role in vertebrate glucose regulation. Here, we examine the evolution of the GCGR family ligand‒receptor systems in different species. Comparatively, we discover that the conserved sequences among GCG family ligands lead to the non-specific activation of ligands across species. In particular, we observe that glucagon-like peptide 1 receptor (GLP1R), glucagon-like peptide 2 receptor (GLP2R), and glucagon-like receptor (GCGLR, also called GCRPR) are arbitrarily activated by other members of the ligand family in birds. Moreover, we reveal that Gallus gallus GLP2 (gGLP2) effectively activates mammalian GLP1R and improves glucose tolerance in diabetic mice. Our study has important implications for understanding blood glucose stabilization in vertebrates and demonstrates that gGLP2 may be a potential drug for treating type 2 diabetes.
基金：
This work was supported by the grants from the National Natural
Science Foundation of China (Nos. 32270438, 32170498, and
31970388), the National Key Research and Development Program
of China (Nos. 2021YFF0702000 and 2018YFD0900602), Science
and Technology Department of Sichuan Province (Nos.2022YFH0116 and 2021YFS0197), 1.3.5 project for disciplines of
excellence, West China Hospital, Sichuan University (No.
ZYJC21050), the Priority Academic Program Development of
Jiangsu Higher Education Institutions (PAPD), and the open and
self-designed project fund of Sichuan Provincial Key Laboratory of
Individualized Medicine Therapy (No. 2021YB06).
第一作者机构：[1]Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Liu Jian,Wang Xue,Zhang WenLi,et al.Evolution of GCGR family ligand‒receptor extensive cross-interaction systems suggests a therapeutic direction for hyperglycemia in mammals[J].ACTA BIOCHIMICA ET BIOPHYSICA SINICA.2023,55(12):1855-1863.doi:10.3724/abbs.2023133.
APA：
Liu Jian,Wang Xue,Zhang WenLi,Liao Guangneng,Shao Zhenhua...&Long Enwu.(2023).Evolution of GCGR family ligand‒receptor extensive cross-interaction systems suggests a therapeutic direction for hyperglycemia in mammals.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,55,(12)
MLA：
Liu Jian,et al."Evolution of GCGR family ligand‒receptor extensive cross-interaction systems suggests a therapeutic direction for hyperglycemia in mammals".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 55..12(2023):1855-1863
