S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Theses (Master's Degree_분자의학 및 바이오제약학과)
Regulation of sortilin expression in skeletal muscle
근육 Sortilin의 발현조절기전
- 융합과학기술대학원 분자의학 및 바이오제약학과
- Issue Date
- 서울대학교 융합과학기술대학원
- Sortilin; trafficking; Glut4; glucose uptake; lysosome degradation; obesity; Type 2 diabetes
- 학위논문 (석사)-- 서울대학교 융합과학기술대학원 분자의학 및 바이오제약학과, 2017. 8. 박경수.
- Sortilin is a multiligand receptor, and belongs to the family of Vps10p domain receptors. Sortilin mainly localizes in the trans-Golgi network and a small amount of sortilin also localizes in the plasma membrane, where sortilin regulates intracellular trafficking, secretion and endocytosis of target proteins. A number of recent studies demonstrated that hepatic sortilin directed ApoB for lysosomal degradation, inhibited ApoB100 secretion, and increased LDL uptake and catabolism, suggesting that hepatic sortilin is involved in lipid metabolism. However, the role of sortilin in skeletal muscle remains unclear.
In this study, I investigated expression levels of sortilin in several tissues from diabetic mice. I found that sortilin protein levels in skeletal muscle were increased in high fat diet (HFD)-induced obese mice and db/db mice, but sortilin levels in liver and adipose tissues were decreased in the diabetic mice.
To figure out what factors regulate sortilin protein levels in diabetic conditions, I tested the effects of several hormones, fatty acids, and cytokines on sortilin protein levels in C2C12 myotubes. Interestingly, sortilin protein was significantly decreased when C2C12 myotubes were maintained in the low level of glucose. The mRNA level of sortilin was not changed by glucose levels, and the stability of sortilin protein was decreased under the low level of glucose. The effect of glucose levels on sortilin stability was not observed in the presence of proteasome inhibitor, suggesting that the low level glucose condition facilitates proteasome-mediated degradation of sortilin. Also, when I determined a physiological role of sortilin according to the glucose levels, sortilin was involved in glucose uptake by insulin stimulated Glut4 translocation in L6-GLUT4myc myotubes.