| Mechanism and regulation of vitamin B2 (riboflavin) uptake by mouse and human pancreatic β-cells/islets: physiological and molecular aspects. | |
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MedLine Citation:
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PMID: 22917629 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Riboflavin (RF) is essential for the normal metabolic activities of pancreatic β-cells and provides protection against oxidative stress. Very little is known about the mechanism of RF uptake by these cells and how the process is regulated. We addressed these issues using mouse-derived pancreatic β-TC-6 cells and freshly isolated primary mouse and human pancreatic islets. Our results showed (3)H-RF uptake by β-TC-6 cells is Na(+) independent, cis inhibited by RF-related compounds, trans stimulated by unlabeled RF, and saturable as a function of concentration (apparent K(m) of 0.17 ± 0.02 μM). The latter findings suggest involvement of a carrier-mediated process. Similarly, RF uptake by primary mouse and human pancreatic islets was via carrier-mediated process. RF transporters 1, 2, and 3 (RFVT-1, -3, and -2) were all expressed in mouse and human pancreatic β-cells/islets, with RFVT-1 being the predominant transporter expressed in the mouse and RFVT-3 in the human. Specific knockdown of RFVT-1 with gene-specific small interfering RNA leads to a significant inhibition in RF uptake by β-TC-6 cells. RF uptake by β-TC-6 cells was also found to be adaptively upregulated in RF deficiency via a transcriptional mechanism(s). Also, the process appears to be under the regulation of a Ca(2+)/calmodulin-mediated regulatory pathway. Results of these studies demonstrate, for the first time, the involvement of a carrier-mediated process for RF uptake by mouse and human pancreatic β-cells/islets. Furthermore, the process appears to be regulated by extracellular and intracellular factors. |
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Authors:
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Abhisek Ghosal; Hamid M Said |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-08-23 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 303 ISSN: 1522-1547 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-05 Completed Date: 2013-01-17 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G1052-8 Citation Subset: IM |
Affiliation:
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Department of Medicine and Physiology/Biophysics, University of California, Irvine, California, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Transport / physiology* Calmodulin / metabolism Cell Line Humans Insulin-Secreting Cells / metabolism*, pathology Islets of Langerhans / metabolism*, pathology Membrane Transport Proteins / metabolism* Mice Nerve Tissue Proteins / metabolism* Oxidation-Reduction / drug effects Oxidative Stress / drug effects Riboflavin* / metabolism, pharmacology Riboflavin Deficiency / metabolism Transcriptional Activation / drug effects, physiology Up-Regulation / drug effects, physiology Vitamin B Complex / metabolism, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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AA 018071/AA/NIAAA NIH HHS; DK56061/DK/NIDDK NIH HHS; DK58057/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Calmodulin; 0/Membrane Transport Proteins; 0/Nerve Tissue Proteins; 0/RFT3 protein, human; 0/riboflavin transporter 1, mouse; 12001-76-2/Vitamin B Complex; 83-88-5/Riboflavin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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