Relative Quantitative Comparison between Lipotoxicity and Glucotoxicity Affecting the PARP-NAD-SIRT1 Pathway in Hepatocytes
Background/Aims: Insulin resistance in type 2 diabetes results from a combination of hyperglycemia and elevated free fatty acid (FFA) concentrations. However, the individual effects of glucotoxicity and lipotoxicity on cell function have not been determined. Methods: To compare the effects of increa...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2013-09-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/354474 |
| _version_ | 1830354918378045440 |
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| author | Jing Pang Chao Xi Junhua Jin Yiwen Han Tie-mei Zhang |
| author_facet | Jing Pang Chao Xi Junhua Jin Yiwen Han Tie-mei Zhang |
| author_sort | Jing Pang |
| collection | DOAJ |
| description | Background/Aims: Insulin resistance in type 2 diabetes results from a combination of hyperglycemia and elevated free fatty acid (FFA) concentrations. However, the individual effects of glucotoxicity and lipotoxicity on cell function have not been determined. Methods: To compare the effects of increased FFAs and glucose levels on the PARP-NAD-SIRT1 pathway, which modulates insulin sensitivity, we cultured HepG2 hepatocytes with 300 or 500 µM oleic acid (OA) or 30 mM glucose for 1-4 days. PARP activity, NAD level, SIRT1 expression and insulin receptor phosphorylation were determined. Results: PARP activity was higher while NAD level and SIRT1 expression were lower in OA-treated cells than in control cells. Insulin receptor phosphorylation in response to insulin stimulation was attenuated under OA stimulation. Compared to glucose, OA produced a more rapid effect on the PARP-NAD-SIRT1 pathway in HepG2 cells. The reduction in SIRT1 expression and insulin receptor phosphorylation was similar in cells treated with 500 μM OA for 1 day and those treated with 30 mM glucose for 4 days. In addition to PARP activation, the LXRα activator T0901317 also affected SIRT1 expression. Conclusion: FFAs modulated cellular function through multiple ways, and induced more rapid and more potent cytotoxicity than glucose. |
| first_indexed | 2024-12-20T01:39:52Z |
| format | Article |
| id | doaj.art-c273baaa1da4412e8c442445e6fc82ac |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-20T01:39:52Z |
| publishDate | 2013-09-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-c273baaa1da4412e8c442445e6fc82ac2022-12-21T19:57:55ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782013-09-0132371972710.1159/000354474354474Relative Quantitative Comparison between Lipotoxicity and Glucotoxicity Affecting the PARP-NAD-SIRT1 Pathway in HepatocytesJing PangChao XiJunhua JinYiwen HanTie-mei ZhangBackground/Aims: Insulin resistance in type 2 diabetes results from a combination of hyperglycemia and elevated free fatty acid (FFA) concentrations. However, the individual effects of glucotoxicity and lipotoxicity on cell function have not been determined. Methods: To compare the effects of increased FFAs and glucose levels on the PARP-NAD-SIRT1 pathway, which modulates insulin sensitivity, we cultured HepG2 hepatocytes with 300 or 500 µM oleic acid (OA) or 30 mM glucose for 1-4 days. PARP activity, NAD level, SIRT1 expression and insulin receptor phosphorylation were determined. Results: PARP activity was higher while NAD level and SIRT1 expression were lower in OA-treated cells than in control cells. Insulin receptor phosphorylation in response to insulin stimulation was attenuated under OA stimulation. Compared to glucose, OA produced a more rapid effect on the PARP-NAD-SIRT1 pathway in HepG2 cells. The reduction in SIRT1 expression and insulin receptor phosphorylation was similar in cells treated with 500 μM OA for 1 day and those treated with 30 mM glucose for 4 days. In addition to PARP activation, the LXRα activator T0901317 also affected SIRT1 expression. Conclusion: FFAs modulated cellular function through multiple ways, and induced more rapid and more potent cytotoxicity than glucose.http://www.karger.com/Article/FullText/354474CytotoxicityFree fatty acidsHyperglycemiaHepatocytesPoly (ADP)-ribose polymerase |
| spellingShingle | Jing Pang Chao Xi Junhua Jin Yiwen Han Tie-mei Zhang Relative Quantitative Comparison between Lipotoxicity and Glucotoxicity Affecting the PARP-NAD-SIRT1 Pathway in Hepatocytes Cellular Physiology and Biochemistry Cytotoxicity Free fatty acids Hyperglycemia Hepatocytes Poly (ADP)-ribose polymerase |
| title | Relative Quantitative Comparison between Lipotoxicity and Glucotoxicity Affecting the PARP-NAD-SIRT1 Pathway in Hepatocytes |
| title_full | Relative Quantitative Comparison between Lipotoxicity and Glucotoxicity Affecting the PARP-NAD-SIRT1 Pathway in Hepatocytes |
| title_fullStr | Relative Quantitative Comparison between Lipotoxicity and Glucotoxicity Affecting the PARP-NAD-SIRT1 Pathway in Hepatocytes |
| title_full_unstemmed | Relative Quantitative Comparison between Lipotoxicity and Glucotoxicity Affecting the PARP-NAD-SIRT1 Pathway in Hepatocytes |
| title_short | Relative Quantitative Comparison between Lipotoxicity and Glucotoxicity Affecting the PARP-NAD-SIRT1 Pathway in Hepatocytes |
| title_sort | relative quantitative comparison between lipotoxicity and glucotoxicity affecting the parp nad sirt1 pathway in hepatocytes |
| topic | Cytotoxicity Free fatty acids Hyperglycemia Hepatocytes Poly (ADP)-ribose polymerase |
| url | http://www.karger.com/Article/FullText/354474 |
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