title: Activated central galanin type 1 receptor alleviated insulin resistance in diabetic rat muscle.
abstract: Evidence indicates that central galanin is involved in regulation of insulin resistance in animals. This study investigates whether type 1 galanin receptor (GAL1) in the brain mediates the ameliorative effect of galanin on insulin resistance in skeletal muscles of type 2 diabetic rats. Rats were intracerebroventricularly (i.c.v.) injected with galanin(1-13)-bradykinin(2-9) amide (M617), a GAL1 agonist, and/or Akti-1/2, an Akt inhibitor, via caudal veins once per day for 10 days. Insulin resistance in muscle tissues was evaluated by glucose tolerance and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) tests, peroxisome proliferator-activated receptor-γ (PPARγ), glucose transporter 4 (GLUT4) mRNA expression levels, Akt phosphorylation, and GLUT4 and vesicle-associated membrane protein 2 (VAMP2) concentration at plasma membranes in muscle cells. The results show that i.c.v. treatment with M617 increased glucose tolerance, 2-NBDG uptake, PPARγ levels, Akt phosphorylation, GLUT4 protein, and GLUT4 mRNA expression levels as well as GLUT4 and VAMP2 concentration at plasma membranes. All increases may be blocked by pretreatment with Akti-1/2. These results suggest that activated central GAL1 may trigger the Akt signaling pathway to alleviate insulin resistance in muscle cells. Therefore, the impact of galanin on insulin resistance is mediated mainly by GAL1 in the brain, and the GAL1 agonist may be taken as a potential antidiabetic agent for treatment of type 2 diabetes mellitus. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Endocrinology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Le
authors.initials: L
authors.lastname: Bu
authors.affiliation: Department of General Surgery, Yancheng City First People's Hospital, Yancheng City, Jiangsu, People's Republic of China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Endocrinology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Sichuan Province of Medicinal Chemistry, Chengdu University, Chengdu, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Endocrinology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Endocrinology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Chunjun
authors.initials: C
authors.lastname: Sheng
authors.affiliation: Department of Endocrinology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D019004:Galanin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D044091:Receptor, Galanin, Type 1 / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; C000614145:M617 peptide; D047495:PPAR gamma; D010446:Peptide Fragments; D044091:Receptor, Galanin, Type 1; C495694:Slc2a4 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; D019004:Galanin; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose; D001920:Bradykinin
keywords: Akt; GLUT4; brain; skeletal muscle; type 1 galanin receptor