| Caveolin-1 is required for vascular endothelial insulin uptake. | |
| | |
MedLine Citation:
|
PMID: 20959538 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
As insulin's movement from plasma to muscle interstitium is rate limiting for its metabolic action, defining the regulation of this movement is critical. Here, we address whether caveolin-1 is required for the first step of insulin's transendothelial transport, its uptake by vascular endothelial cells (ECs), and whether IL-6 and TNFα affect insulin uptake or caveolin-1 expression. Uptake of FITC-labeled insulin was measured using confocal microscopy in control bovine aortic ECs (bAECs), in bAECs in which caveolin-1 was either knocked down or overexpressed, in murine ECs from caveolin-1(-/-) mice and in bAECs exposed to inflammatory cytokines. Knockdown of caveolin-1 expression in bAECs using specific caveolin-1 siRNA reduced caveolin-1 mRNA and protein expression by ∼ 70%, and reduced FITC-insulin uptake by 67% (P < 0.05 for each). Over-expression of caveolin-1 increased insulin uptake (P < 0.05). Caveolin-1-null mouse aortic ECs did not take up insulin and re-expression of caveolin-1 by transfecting these cells with FLAG-tagged caveolin-1 DNA rescued FITC-insulin uptake. Knockdown of caveolin-1 significantly reduced both insulin receptor protein level and insulin-stimulated Akt1 phosphorylation. Knockdown of caveolin-1 also inhibited insulin-induced caveolin-1 and IGF-1 receptor translocation to the plasma membrane. Compared with controls, IL-6 or TNFα (20 ng/ml for 24 h) inhibited FITC-insulin uptake as well as the expression of caveolin-1 mRNA and protein (P < 0.05 for each). IL-6 or TNFα also significantly reduced plasma membrane-associated caveolin-1. Thus, we conclude that insulin uptake by ECs requires expression of caveolin-1 supporting a role for caveolae mediating insulin uptake. Proinflammatory cytokines may inhibit insulin uptake, at least in part, by inhibiting caveolin-1 expression. |
| | |
Authors:
|
Hong Wang; Aileen X Wang; Eugene J Barrett |
Related Documents
:
|
20181658 - 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs an insulin signaling pathway through the in... 19962298 - Effects of a grapeseed procyanidin extract (gspe) on insulin resistance. 19406948 - Caveolin-1 loss of function accelerates glucose transporter 4 and insulin receptor degr... 12091438 - Glucose-induced activation of glucose uptake in cells from the inner and outer blood-re... 11458678 - Arterial baroreceptors and experimental diabetes. 3666048 - Insulin-dependent diabetes: strategy for immune intervention. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-19 |
Journal Detail:
|
Title: American journal of physiology. Endocrinology and metabolism Volume: 300 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2010-12-29 Completed Date: 2011-01-31 Revised Date: 2012-02-06 |
Medline Journal Info:
|
Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
|
Languages: eng Pagination: E134-44 Citation Subset: IM |
Affiliation:
|
Division of Endocrinology and Metablism, Department of Internal Medicine, University of Virginia Health System, P.O. Box 801410, 450 Ray C. Hunt Dr., Charlottesville, VA 22908, USA. hw8t@Virginia.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Aorta / cytology, metabolism Biological Transport Cattle Caveolin 1 / genetics, physiology* Cell Membrane / metabolism Cells, Cultured Endothelium, Vascular / cytology, metabolism* Gene Expression Inflammation Mediators / metabolism Insulin / metabolism* Mice Mice, Knockout Phosphorylation Protein Transport Proto-Oncogene Proteins c-akt / metabolism RNA, Messenger / metabolism RNA, Small Interfering Receptor, Insulin / metabolism Tumor Necrosis Factor-alpha / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
DK-057878/DK/NIDDK NIH HHS; DK-073059/DK/NIDDK NIH HHS; R01 DK057878-12/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Caveolin 1; 0/Inflammation Mediators; 0/Insulin; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Tumor Necrosis Factor-alpha; EC 2.7.10.1/Receptor, Insulin; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reducing selenoprotein P expression suppresses adipocyte differentiation as a result of increased pr...
Next Document: Peripheral arterial occlusive disease: evaluation of a high spatial and temporal resolution 3-T MR p...