Resistin induces insulin resistance by both AMPK-dependent and AMPK-independent mechanisms in HepG2 cells
- PDF / 640,688 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 50 Downloads / 160 Views
ORIGINAL ARTICLE
Resistin induces insulin resistance by both AMPK-dependent and AMPK-independent mechanisms in HepG2 cells Zhaofan Luo Æ Ying Zhang Æ Fangping Li Æ Juan He Æ Helin Ding Æ Li Yan Æ Hua Cheng
Received: 30 December 2008 / Accepted: 8 April 2009 / Published online: 8 May 2009 Ó Humana Press 2009
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 AMPKa2 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 glucose6-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
Z. Luo Y. Zhang F. Li J. He H. Ding L. Yan H. Cheng Department of Endocrinology, The Second Affiliated Hospital, Sun Yat-Sen University, 510120 Guangzhou, People’s Republic of China F. Li (&) Endocrinology and Metabolism Department, The Second Affiliated Hospital, Sun Yat-sen University, 107 Yanjiang West Road, 510120 Guangzhou, People’s Republic of China e-mail: [email protected]
glucose production via AMPK-mediated upregulated expression of the genes encoding hepatic gluconeogenic enzymes, G6Pase, and PEPCK. Keywords AMPK Diabetes Insulin Resistin siRNA HepG2
Introduction Obesity is closely correlated with type 2 diabetes mellitus and insulin resistance [1, 2]; however, the underlying mechanisms have not been fully elucidated. There is evidence, both in vitro and in vivo, that adipose tissue can be regarded as a major secretory and endocrine organ and that a variety of factors released by adipose cells potentially mediate insulin resistance [3, 4]. TNFa, leptin, adiponectin, MCP-1, resistin, and several other adipokines are thought to be involved in the regulation of glucose metabolism and insulin sensitivity. Resistin, as an adipocyte-secreted factor and Fizz3 [5, 6], has been postulated to link obesity and diabetes in a rodent model of disease [7]. Findings from in vivo studies indicate that infusion of resistin dramatica
Data Loading...
