title: Blocking central galanin receptors attenuates insulin sensitivity in myocytes of diabetic trained rats.
abstract: Galanin (Gal), a bioactive neuropeptide, is widely distributed throughout the central nervous system and has diverse modulatory effects. To understand the central effect of this training-stimulatory peptide on insulin sensitivity, its antagonist M35 was injected into the cerebral ventricle in type 2 diabetic rats. A treadmill running of the rats was used to stimulate circulating Gal secretion and central Gal mRNA expression. The results showed that M35 significantly decreased glucose infusion rates in euglycemic-hyperinsulinemic clamp tests as well as 2-deoxy-[(3) H]D-glucose uptake and peroxisome proliferator-activated receptor-α expression levels in skeletal muscles. M35 also attenuated glucose transporter 4 (GLUT4) concentration in plasma membranes and total cell membranes of myocytes, and the ratios of the GLUT4 contents in the former to the latter in M35 groups were lower than those of each diabetic control. These results imply that endogenous Gal, acting through its central receptor, may facilitate GLUT4 translocation from cytoplasm vesicles to cellular surface of myocytes to accelerate glucose uptake and to enhance insulin sensitivity in healthy and type 2 diabetic rats. Gal and its relative agents are potential targets for treatment of type 2 diabetes mellitus and its complications.
authors: Department of Endocrinology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai, China. lebu2000@sina.cn
authors: Le
authors: L
authors: Bu
authors: Zhimin
authors: Z
authors: Liu
authors: Junjie
authors: J
authors: Zou
authors: Xiang
authors: X
authors: Gao
authors: Yi
authors: Y
authors: Bao
authors: Shen
authors: S
authors: Qu
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D003847:Deoxyglucose; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005080:Exercise Test; D019004:Galanin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D047493:PPAR alpha / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044088:Receptors, Galanin / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity; D014316:Tritium
chemical_list: D051275:Glucose Transporter Type 4; D047493:PPAR alpha; D010446:Peptide Fragments; D012333:RNA, Messenger; D044088:Receptors, Galanin; D014316:Tritium; C074069:galanin-(1-13)-bradykinin-(2-9)-amide; D013311:Streptozocin; D019004:Galanin; D003847:Deoxyglucose; D001920:Bradykinin