title: Glucose deprivation attenuates sortilin levels in skeletal muscle cells.
abstract: In skeletal muscle, sortilin plays a predominant role in the sorting of glucose transporter 4 (Glut4), thereby controlling glucose uptake. Moreover, our previous study suggested that the sortilin expression levels are also implicated in myogenesis. Despite the importance of sortilin in skeletal muscle, however, the regulation of sortilin expression has not been completely understood. In the present study, we analyzed if the sortilin expression is regulated by glucose in C2C12 myocytes and rat skeletal muscles in vivo. Sortilin protein expression was elevated upon C2C12 cell differentiation and was further enhanced in the presence of a high concentration of glucose. The gene expression and protein degradation of sortilin were not affected by glucose. On the other hand, rapamycin partially reduced sortilin induction by a high concentration of glucose, which suggested that sortilin translation could be regulated by glucose, at least in part. We also examined if the sortilin regulation by glucose was also observed in skeletal muscles that were obtained from fed or fasted rats. Sortilin expression in both gastrocnemius and extensor digitorum longus (EDL) muscle was significantly decreased by 17-18h of starvation. On the other hand, pathological levels of high blood glucose did not alter the sortilin expression in rat skeletal muscle. Overall, the present study suggests that sortilin protein levels are reduced under hypoglycemic conditions by post-transcriptional control in skeletal muscles.
authors.affiliation: Department of Animal Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Ariga
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yoneyama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Fukushima
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ishiuchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishii
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sato
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hakuno
authors.forename: Taku
authors.initials: T
authors.lastname: Nedachi
authors.forename: Shin-Ichiro
authors.initials: SI
authors.lastname: Takahashi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D002454:Cell Differentiation; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005215:Fasting / Q000378:metabolism*; D005508:Food Deprivation; D005947:Glucose / Q000378:metabolism; D006614:Hindlimb; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001786:Blood Glucose; D005947:Glucose; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D000099183:Sortilin