Resistin is expressed in human hepatocytes and induces insulin resistance.
Resistin, known as an adipocyte-specific secretory factor (ADSF), is implicated to modulate insulin resistance in rodents. However, the precise role of this factor for human insulin resistance has remained elusive. Here, we investigate the relationship between human resistin and insulin resistance in hepatocytes and the effect of Metformin on resistin. In this study, the expression of resistin in human hepatocytes and hepatic tissues was examined, and the human resistin eukaryotic expression vector was constructed and stably transfected in HepG2 cells. Data showed that resistin is expressed in human hepatocytes and hepatic tissues. Overexpression of human resistin impaired significantly insulin-stimulated glucose uptake and glycogen synthesis in HepG2 cells. It also decreased the expression of insulin receptor substrate 2 (IRS-2) and c-cbl associated protein (CAP), whereas increased the expression of glycogen synthetase kinase 3beta (GSK-3beta). The result suggested that human resistin induced insulin resistance in hepatocytes by blocking the two insulin signal transduction pathways of PI-3K/Akt and of CAP/c-cbl. We also concluded that Metformin reversed the effect of resistin and downregulated the expression of resistin in hepatocytes.
Sheng
Chun Hua
CH
Department of Central Research, The Third Clinical College, Jilin University, Xiantai Street No. 126, Changchun, 130033, China.
Di
Jun
J
Jin
Yong
Y
Zhang
Yu Cheng
YC
Wu
Mei
M
Sun
Ying
Y
Zhang
Gui Zhen
GZ
D015153:Blotting, Western; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology; D010503:Periodic Acid-Schiff Reaction; D010957:Plasmids; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D052243:Resistin / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D052243:Resistin; D008687:Metformin; D005947:Glucose