Apolipoprotein A-I stimulates AMP-activated protein kinase and improves glucose metabolism

R. Han, R. Lai, Q. Ding, Z. Wang, X. Luo, Y. Zhang, G. Cui, J. He, W. Liu, Y. Chen

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

Aims/hypothesis: 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/interpretation: 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.

Original languageEnglish (US)
Pages (from-to)1960-1968
Number of pages9
JournalDiabetologia
Volume50
Issue number9
DOIs
StatePublished - Sep 2007

Bibliographical note

Funding Information:
Acknowledgements We wish to thank Y. Liu and L. Dong for technical assistance. This work was supported by research grants from Chinese Academy of Sciences (One Hundred Talents Program and The Knowledge Innovation Program KSCX1-YW-02), National Natural Science Foundation of China (30588002 and 30470870), Science and Technology Commission of Shanghai Municipality (04dz14007), Ministry of Science and Technology of China (2006CB503900 and 2006CB943902) and ‘Western Light’ Program of Talent to Y. Chen.

Keywords

  • AMP-activated protein kinase
  • AMPK
  • APOA-I
  • Apolipoprotein A-I
  • Endocytosis
  • Fat mass
  • Glucose homeostasis
  • Insulin resistance
  • Type 2 diabetes

Fingerprint Dive into the research topics of 'Apolipoprotein A-I stimulates AMP-activated protein kinase and improves glucose metabolism'. Together they form a unique fingerprint.

Cite this