| NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions. | |
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MedLine Citation:
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PMID: 20739506 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise. |
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Authors:
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Puntip Tantiwong; Karthigayan Shanmugasundaram; Adriana Monroy; Sangeeta Ghosh; Mengyao Li; Ralph A DeFronzo; Eugenio Cersosimo; Apiradee Sriwijitkamol; Sumathy Mohan; Nicolas Musi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-08-24 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 299 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-27 Completed Date: 2010-11-16 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E794-801 Citation Subset: IM |
Affiliation:
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Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Blood Glucose / metabolism Blotting, Western Caspase 8 / biosynthesis, genetics Chemokine CCL2 / biosynthesis, genetics Diabetes Mellitus, Type 2 / metabolism* Exercise / physiology* Fatty Acids, Nonesterified / blood Female Humans Insulin / blood Interleukin-6 / biosynthesis, genetics Male Middle Aged Muscle, Skeletal / metabolism* NF-kappa B / metabolism* Obesity / metabolism* Oxygen Consumption RNA, Messenger / chemistry, genetics Reverse Transcriptase Polymerase Chain Reaction Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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AG-030979/AG/NIA NIH HHS; CA-112175/CA/NCI NIH HHS; DK-24092/DK/NIDDK NIH HHS; DK-80157/DK/NIDDK NIH HHS; T32-HL-04776/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/CCL2 protein, human; 0/Chemokine CCL2; 0/Fatty Acids, Nonesterified; 0/Interleukin-6; 0/NF-kappa B; 0/RNA, Messenger; 11061-68-0/Insulin; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Caspase 8 |
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