Glucose deprivation attenuates sortilin levels in skeletal muscle cells

• Published in: Endocrine Journal 2017, Vol.64(3), pp.255-268
• Main Authors: Ariga, Miyako, Yoneyama, Yosuke, Fukushima, Toshiaki, Ishiuchi, Yuri, Ishii, Takayuki, Sato, Hitoshi, Hakuno, Fumihiko, Nedachi, Taku, Takahashi, Shin-Ichiro
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Vesicular Transport - agonists; Adaptor Proteins, Vesicular Transport - genetics; Adaptor Proteins, Vesicular Transport - metabolism; AMPK; Animals; Blood Glucose - analysis; Cell Differentiation; Cell Line; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Down-Regulation - drug effects; Fasting - metabolism; Food Deprivation; Gene expression; Glucose; Glucose - metabolism; Glucose transporter; Hindlimb; Hyperglycemia; Male; Mechanistic Target of Rapamycin Complex 1; Multiprotein Complexes - antagonists & inhibitors; Multiprotein Complexes - metabolism; Muscle Cells - cytology; Muscle Cells - drug effects; Muscle Cells - metabolism; Muscle Cells - pathology; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Musculoskeletal system; Myocytes; Myogenesis; Post-transcription; Protein Kinase Inhibitors - pharmacology; Proteins; Rapamycin; Rats, Wistar; RNA, Messenger - metabolism; Rodents; Sirolimus - pharmacology; Skeletal muscle; Sortilin; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism; Up-Regulation - drug effects
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.EJ16-0319

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.