A natural compound jaceosidin ameliorates endoplasmic reticulum stress and insulin resistance via upregulation of SERCA2b.
Increased endoplasmic reticulum (ER) stress has emerged as a vital contributor to dysregulated glucose homeostasis, and impaired function of sarco-endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) is one of the central mechanisms underlying ER stress. In this study, we reported that SERCA2b upregulation contributed to the amelioration of ER stress and insulin resistance by a small natural compound jaceosidin. In a model of differentiated C2C12 myotubes, jaceosidin-triggered SERCA2b upregulation enhanced insulin sensitivity and decreased ER stress. Moreover, the activity of Ca2+-ATPase in thapsigargin-treated myotubes was also augmented by jaceosidin. Furthermore, jaceosidin significantly suppressed blood glucose levels, improved glucose tolerance and lowered body weight, but did not alter food intake in insulin-resistant obese mice. In addition, this compound markedly reduced lipid accumulation, suppressed the expression of lipogenic genes in liver and ameliorated liver injury. The ameliorative effects of jaceosidin were due to its ability to reduce ER stress via increasing the expression of SERCA2b in the muscles of obese mice. Taken together, jaceosidin could improve ER stress and attenuate insulin resistance via SERCA2b upregulation in mice skeletal muscles.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Zijun
Z
Ouyang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Wanshuai
W
Li
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Qianqian
Q
Meng
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Qi
Q
Zhang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Xingqi
X
Wang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Ahmed
A
Elgehama
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Xudong
X
Wu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Yan
Y
Shen
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Yang
Y
Sun
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. Electronic address: wuxf@nju.edu.cn.
Xuefeng
X
Wu
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. Electronic address: molpharm@163.com.
Qiang
Q
Xu
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D001786:Blood Glucose; D005419:Flavonoids; C477508:jaceosidin; D019284:Thapsigargin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases
Insulin resistance; Jaceosidin; Obesity; SERCA2b; Skeletal muscle