| Resistin induces insulin resistance by both AMPK-dependent and AMPK-independent mechanisms in HepG2 cells. | |
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MedLine Citation:
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PMID: 19440859 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 AMPKalpha2 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-(14)C] 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. |
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Authors:
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Zhaofan Luo; Ying Zhang; Fangping Li; Juan He; Helin Ding; Li Yan; Hua Cheng |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-08 |
Journal Detail:
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Title: Endocrine Volume: 36 ISSN: 1355-008X ISO Abbreviation: Endocrine Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-07-07 Completed Date: 2009-10-01 Revised Date: 2010-06-24 |
Medline Journal Info:
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Nlm Unique ID: 9434444 Medline TA: Endocrine Country: United States |
Other Details:
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Languages: eng Pagination: 60-9 Citation Subset: IM |
Affiliation:
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Department of Endocrinology, The Second Affiliated Hospital, Sun Yat-Sen University, 510120, Guangzhou, People's Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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genetics,
metabolism* Carcinoma, Hepatocellular / metabolism*, pathology Cell Line, Tumor Gene Expression / drug effects, physiology Glucaric Acid / metabolism Glucose Transporter Type 2 / genetics Glucose-6-Phosphatase / genetics Glycogen / biosynthesis Humans Hypoglycemic Agents / metabolism, pharmacology Insulin / metabolism, pharmacology Insulin Receptor Substrate Proteins / genetics Insulin Resistance / physiology Liver Neoplasms / metabolism*, pathology Phosphoenolpyruvate Carboxykinase (GTP) / genetics Phosphorylation / drug effects, physiology Proto-Oncogene Proteins c-akt / metabolism RNA, Small Interfering Resistin / metabolism*, pharmacology Signal Transduction / drug effects, physiology Suppressor of Cytokine Signaling Proteins / genetics |
| Chemical | |
Reg. No./Substance:
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0/Glucose Transporter Type 2; 0/Hypoglycemic Agents; 0/IRS2 protein, human; 0/Insulin Receptor Substrate Proteins; 0/RETN protein, human; 0/RNA, Small Interfering; 0/Resistin; 0/SLC2A2 protein, human; 0/SOCS3 protein, human; 0/Suppressor of Cytokine Signaling Proteins; 11061-68-0/Insulin; 25525-21-7/Glucaric Acid; 9005-79-2/Glycogen; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/PRKAA2 protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.9/Glucose-6-Phosphatase; EC 4.1.1.32/Phosphoenolpyruvate Carboxykinase (GTP) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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