Apolipoprotein A-I stimulates AMP-activated protein kinase and improves glucose metabolism.
OBJECTIVE
In humans, one of the hallmarks of type 2 diabetes is a reduced plasma concentration of HDL and its major protein component, apolipoprotein A-I (APOA-I). However, it is unknown whether APOA-I directly protects against diabetes. The aim of this study was to characterise the functional role of APOA-I in glucose homeostasis.


METHODS
The effects of APOA-I on phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC), glucose uptake and endocytosis were analysed in C2C12 myocytes. Glucose metabolism was investigated in Apoa-I knockout (Apoa-I (-/-)) mice.


RESULTS
APOA-I was able to stimulate the phosphorylation of AMPK and ACC, and elevated glucose uptake in C2C12 myocytes. APOA-I could be endocytosed into C2C12 myotubes through a clathrin-dependent endocytotic process. Inhibition of endocytosis abrogated APOA-I-stimulated AMPK phosphorylation. In Apoa-I (-/-) mice, AMPK phosphorylation was reduced in skeletal muscle and liver, and expression of gluconeogenic enzymes was increased in liver. In addition, the Apoa-I (-/-) mice had increased fat content and compromised glucose tolerance.


CONCLUSIONS
Our data indicate that APOA-I has a protective effect against diabetes via activation of AMPK. ApoA-I deletion in the mouse led to increased fat mass and impaired glucose tolerance.
Han
R
R
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China.
Lai
R
R
Department of Biochemistry and Molecular Biology, Gannan Medical College, Ganzhou, Jiangxi, 341000, China.
Ding
Q
Q
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China.
Wang
Z
Z
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China.
Luo
X
X
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China.
Zhang
Y
Y
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China.
Cui
G
G
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China.
He
J
J
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China.
Liu
W
W
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China.
Chen
Y
Y
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, 200031, China. ychen3@sibs.ac.cn.
D055372:AMP-Activated Protein Kinases; D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D002460:Cell Line; D003847:Deoxyglucose / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D009097:Multienzyme Complexes / Q000187:drug effects / Q000378:metabolism*; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism*
D016632:Apolipoprotein A-I; D009097:Multienzyme Complexes; D003847:Deoxyglucose; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose