Astragalus polysaccharide suppresses skeletal muscle myostatin expression in diabetes: involvement of ROS-ERK and NF-κB pathways.
OBJECTIVE
The antidiabetes drug astragalus polysaccharide (APS) is capable of increasing insulin sensitivity in skeletal muscle and improving whole-body glucose homeostasis. Recent studies suggest that skeletal muscle secreted growth factor myostatin plays an important role in regulating insulin signaling and insulin resistance. We hypothesized that regulation of skeletal muscle myostatin expression may be involved in the improvement of insulin sensitivity by APS.


METHODS
APS was administered to 13-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Complementary studies examined APS effects on the saturated acid palmitate-induced insulin resistance and myostatin expression in C2C12 cells.


RESULTS
APS treatment ameliorated hyperglycemia, hyperlipidemia, and insulin resistance and decreased the elevation of myostatin expression and malondialdehyde production in skeletal muscle of noninsulin-dependent diabetic KKAy mice. In C2C12 cells in vitro, saturated acid palmitate-induced impaired glucose uptake, overproduction of ROS, activation of extracellular regulated protein kinases (ERK), and NF-κB were partially restored by APS treatment. The protective effects of APS were mimicked by ERK and NF-κB inhibitors, respectively.


CONCLUSIONS
Our study demonstrates elevated myostatin expression in skeletal muscle of type 2 diabetic KKAy mice and in cultured C2C12 cells exposed to palmitate. APS is capable of improving insulin sensitivity and decreasing myostatin expression in skeletal muscle through downregulating ROS-ERK-NF-κB pathway.
Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071, China ; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Min
M
Liu
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Jian
J
Qin
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Yarong
Y
Hao
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Min
M
Liu
Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Jun
J
Luo
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Tao
T
Luo
Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071, China.
Lei
L
Wei
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005227:Fatty Acids / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D007333:Insulin Resistance; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D001786:Blood Glucose; D005227:Fatty Acids; D055435:Myostatin; D016328:NF-kappa B; D011134:Polysaccharides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019308:Palmitic Acid; D008315:Malondialdehyde; D048049:Extracellular Signal-Regulated MAP Kinases