Document Detail


Mechanism and regulation of vitamin B2 (riboflavin) uptake by mouse and human pancreatic β-cells/islets: physiological and molecular aspects.
MedLine Citation:
PMID:  22917629     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Abhisek Ghosal; Hamid M Said
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Publication Detail:
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:
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:
Created Date:  2012-11-05     Completed Date:  2013-01-17     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G1052-8     Citation Subset:  IM    
Affiliation:
Department of Medicine and Physiology/Biophysics, University of California, Irvine, California, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
AA 018071/AA/NIAAA NIH HHS; DK56061/DK/NIDDK NIH HHS; DK58057/DK/NIDDK NIH HHS; R01 DK058057/DK/NIDDK NIH HHS; R37 DK056061/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
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
Comments/Corrections

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