دورية أكاديمية
أعرض في EDS

Paracrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects.

التفاصيل البيبلوغرافية
العنوان: Paracrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects.
المؤلفون: Ying L; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.; School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Wang L; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Guo K; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Hou Y; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Li N; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.; School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Wang S; Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Liu X; 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.; Diabetes Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.; CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China., Zhao Q; 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.; Diabetes Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.; CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China., Zhou J; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Zhao L; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Niu J; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Chen C; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Song L; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Hou S; 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.; Diabetes Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.; CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China., Kong L; 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.; Diabetes Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.; CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China., Li X; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China., Ren J; Department of Cardiology and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. jren_aldh2@outlook.com., Li P; 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. lipp@imm.ac.cn.; Diabetes Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. lipp@imm.ac.cn.; CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. lipp@imm.ac.cn., Mohammadi M; Department of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA. mohammadimoosa@gmail.com., Huang Z; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. hzf@wmu.edu.cn.
المصدر: Nature communications [Nat Commun] 2021 Dec 14; Vol. 12 (1), pp. 7256. Date of Electronic Publication: 2021 Dec 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Fibroblast Growth Factor 4/*pharmacology , Hypoglycemic Agents/*pharmacology , Muscle, Skeletal/*drug effects, AMP-Activated Protein Kinases/metabolism ; Animals ; Calcium-Calmodulin-Dependent Protein Kinase Kinase ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Fibroblast Growth Factor 4/administration & dosage ; Fibroblast Growth Factor 4/metabolism ; Fibroblast Growth Factors/administration & dosage ; Fibroblast Growth Factors/metabolism ; Fibroblast Growth Factors/pharmacology ; Glucose/metabolism ; Glucose Transporter Type 4/metabolism ; Humans ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/metabolism ; Inflammation ; Insulin Resistance ; Ligands ; Macrophages/drug effects ; Macrophages/metabolism ; Mice ; Muscle, Skeletal/metabolism ; Obesity/drug therapy ; Obesity/metabolism ; Paracrine Communication ; Receptor, Fibroblast Growth Factor, Type 1/metabolism ; Signal Transduction/drug effects
مستخلص: Several members of the FGF family have been identified as potential regulators of glucose homeostasis. We previously reported that a low threshold of FGF-induced FGF receptor 1c (FGFR1c) dimerization and activity is sufficient to evoke a glucose lowering activity. We therefore reasoned that ligand identity may not matter, and that besides paracrine FGF1 and endocrine FGF21, other cognate paracrine FGFs of FGFR1c might possess such activity. Indeed, via a side-by-side testing of multiple cognate FGFs of FGFR1c in diabetic mice we identified the paracrine FGF4 as a potent anti-hyperglycemic FGF. Importantly, we found that like FGF1, the paracrine FGF4 is also more efficacious than endocrine FGF21 in lowering blood glucose. We show that paracrine FGF4 and FGF1 exert their superior glycemic control by targeting skeletal muscle, which expresses copious FGFR1c but lacks β-klotho (KLB), an obligatory FGF21 co-receptor. Mechanistically, both FGF4 and FGF1 upregulate GLUT4 cell surface abundance in skeletal muscle in an AMPKα-dependent but insulin-independent manner. Chronic treatment with rFGF4 improves insulin resistance and suppresses adipose macrophage infiltration and inflammation. Notably, unlike FGF1 (a pan-FGFR ligand), FGF4, which has more restricted FGFR1c binding specificity, has no apparent effect on food intake. The potent anti-hyperglycemic and anti-inflammatory properties of FGF4 testify to its promising potential for use in the treatment of T2D and related metabolic disorders.
(© 2021. The Author(s).)
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المشرفين على المادة: 0 (Fibroblast Growth Factor 4)
0 (Glucose Transporter Type 4)
0 (Hypoglycemic Agents)
0 (Ligands)
62031-54-3 (Fibroblast Growth Factors)
EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1)
EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
IY9XDZ35W2 (Glucose)
تواريخ الأحداث: Date Created: 20211215 Date Completed: 20220110 Latest Revision: 20220110
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8671394
DOI: 10.1038/s41467-021-27584-y
PMID: 34907199
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-021-27584-y