| Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-α and interleukin-6. | |
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MedLine Citation:
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PMID: 21062957 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Obesity is often associated with insulin resistance, low-grade systemic inflammation, and reduced plasma adiponectin. Inflammation is also increased in adipose tissue, but it is not clear whether the reductions of adiponectin levels are related to dysregulation of insulin activity and/or increased proinflammatory mediators. In this study, we investigated the interactions of insulin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in the regulation of adiponectin production using in vivo and in vitro approaches. Plasma adiponectin and parameters of insulin resistance and inflammation were assessed in a cohort of lean and obese insulin-resistant subjects. In addition, the effect of insulin was examined in vivo using the hyperinsulinemic-euglycemic clamp, and in adipose tissue (AT) cultures. Compared with lean subjects, the levels of total adiponectin, and especially the high-molecular-weight (HMW) isomer, were abnormally low in obese insulin-resistant subjects. The hyperinsulinemic clamp data confirmed the insulin-resistant state in the obese patients and showed that insulin infusion significantly increased the plasma adiponectin in lean but not obese subjects (P < 0.01). Similarly, insulin increased total adiponectin release from AT explants of lean and not obese subjects. Moreover, expression and secretion of TNF-α and IL-6 increased significantly in AT of obese subjects and were negatively associated with expression and secretion of adiponectin. In 3T3-L1 and human adipocyte cultures, insulin strongly enhanced adiponectin expression (2-fold) and secretion (3-fold). TNF-α, and not IL-6, strongly opposed the stimulatory effects of insulin. Intriguingly, the inhibitory effect of TNF-α was especially directed toward the HMW isomer of adiponectin. In conclusion, these studies show that insulin upregulates adiponectin expression and release, and that TNF-α opposes the stimulatory effects of insulin. A combination of insulin resistance and increased TNF-α production could explain the decline of adiponectin levels and alterations of isomer composition in plasma of obese insulin-resistant subjects. |
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Authors:
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Tahar Hajri; Huan Tao; Julia Wattacheril; Pamela Marks-Shulman; Naji N Abumrad |
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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 Date: 2010-11-09 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 300 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-28 Completed Date: 2011-03-03 Revised Date: 2012-02-21 |
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: E350-60 Citation Subset: IM |
Affiliation:
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Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA. tahar.hajri@vanderbilt.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3-L1 Cells Adipocytes / drug effects, metabolism Adiponectin / biosynthesis* Adipose Tissue / metabolism Adult Animals Body Mass Index Cell Differentiation / physiology Cell Separation Culture Media Cytokines / blood Female Glucose Clamp Technique Humans Hypoglycemic Agents / pharmacology* Insulin / pharmacology* Insulin Resistance Interleukin-6 / pharmacology* Male Mice Middle Aged Obesity / metabolism Organ Culture Techniques Receptors, Adiponectin / metabolism Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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DK-070860-01S1/DK/NIDDK NIH HHS; R01 DK070860-05/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Culture Media; 0/Cytokines; 0/Hypoglycemic Agents; 0/Insulin; 0/Interleukin-6; 0/Receptors, Adiponectin; 0/Tumor Necrosis Factor-alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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