Endocrine

, Volume 36, Issue 1, pp 60–69 | Cite as

Resistin induces insulin resistance by both AMPK-dependent and AMPK-independent mechanisms in HepG2 cells

  • Zhaofan Luo
  • Ying Zhang
  • Fangping Li
  • Juan He
  • Helin Ding
  • Li Yan
  • Hua Cheng
Original Article

Abstract

Resistin is a 12.5-KDa cysteine-rich peptide that has been implicated in the impairment of glucose homeostasis via the AMP-activated protein kinase (AMPK) pathway in a rodent model. However, the role resistin plays in humans is controversial. This study investigated the effect of resistin on glucose metabolism and insulin signaling using human recombinant resistin and small interfering RNA (siRNA) against AMPKα2 to treat the human liver HepG2 cells. The mRNA of key genes involved in glucose metabolism and the insulin-signaling pathway were detected by real-time RT-PCR. Phosphorylation levels of Akt and AMPK were measured by western blot. The incorporation of D-[U–14C] glucose into glycogen was quantitated by liquid scintillation counting. The results demonstrate that resistin stimulated expressions of glucose-6-phosphatase (G6Pase), phosphoenolypyruvate carboxykinase (PEPCK), and suppressor of cytokine signaling 3 (SOCS-3), repressed the expressions of insulin receptor substrate 2(IRS-2) and glucose transporter 2(GLUT2). In addition, resistin inhibited the insulin-induced phosphorylation of Akt independent of AMPK. In conclusion, our findings suggest that resistin induces insulin resistance in HepG2 cells at least partly via induction of SOCS-3 expression and reduction of Akt phosphorylation through an AMPK-independent mechanism. Resistin also increases glucose production via AMPK-mediated upregulated expression of the genes encoding hepatic gluconeogenic enzymes, G6Pase, and PEPCK.

Keywords

AMPK Diabetes Insulin Resistin siRNA HepG2 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Zhaofan Luo
    • 1
  • Ying Zhang
    • 1
  • Fangping Li
    • 1
    • 2
  • Juan He
    • 1
  • Helin Ding
    • 1
  • Li Yan
    • 1
  • Hua Cheng
    • 1
  1. 1.Department of Endocrinology, The Second Affiliated HospitalSun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  2. 2.Endocrinology and Metabolism Department, The Second Affiliated HospitalSun Yat-sen UniversityGuangzhouPeople’s Republic of China

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