title: Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle insulin resistance through the Akt/AS160/GLUT4 pathway.
abstract: Insulin resistance of skeletal muscle plays an important role in the pathogenesis of type 2 diabetes. Galanin, a 29/30-amino-acid neuropeptide, plays multiple biological actions, including anti-diabetic effects. Although recent results of our study showed that administration of galanin could mitigate insulin resistance by promoting glucose transporter 4 (GLUT4) expression and translocation in skeletal muscle of rats, there is no literature available regarding to the effect of type 1 of galanin receptors (GALR1) on insulin resistance in skeletal muscle of type 2 diabetic rats. Herein, we intended to survey the central effect of GALR1 agonist M617 on insulin resistance in skeletal muscle and its underlying mechanisms. We found that the intracerebroventricular injection of M617 increased glucose infusion rates in hyperinsulinemic euglycemic clamp tests, but attenuated the plasma insulin and glucose concentrations of diabetic rats. Furthermore, administration of M617 markedly increased GLUT4 mRNA expression and GLUT4 translocation in skeletal muscle of diabetic rats. Last, perfusion of M617 increased phosphorylated Akt and phosphorylated AS160 levels in the skeletal muscle of diabetic rats. In conclusion, central injection of M617 mitigated insulin resistance of skeletal muscle by enhancing GLUT4 translocation from intracellular pools to plasma membranes via the activation of the Akt/AS160/GLUT4 signaling pathway.
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China; Department of Physiology, Nanjing University of Chinese Medicine Hanlin College, Taizhou, Jiangsu 225300, China.
authors.forename: Penghua
authors.initials: P
authors.lastname: Fang
authors.affiliation: Department of Physiology, Nanjing University of Chinese Medicine Hanlin College, Taizhou, Jiangsu 225300, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China.
authors.forename: Biao
authors.initials: B
authors.lastname: He
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Guo
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China.
authors.forename: Guimei
authors.initials: G
authors.lastname: Kong
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China; Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China. Electronic address: boping@yzu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Bo
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China; Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China. Electronic address: physiolpep@sina.cn.
authors.forename: Zhenwen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D019004:Galanin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044091:Receptor, Galanin, Type 1 / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; C000614145:M617 peptide; D010446:Peptide Fragments; D044091:Receptor, Galanin, Type 1; C495694:Slc2a4 protein, rat; C533101:TBC1D4 protein, rat; D019004:Galanin; D051057:Proto-Oncogene Proteins c-akt; D001920:Bradykinin
keywords: GALR1; GLUT4; M617; Skeletal muscle