title: Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process.
abstract: Biotin is essential for the normal function of pancreatic beta cells. These cells obtain biotin from their surroundings via transport across their cell membrane. Little is known about the uptake mechanism involved, how it is regulated, and how it is affected by internal and external factors. We addressed these issues using the mouse-derived pancreatic beta-TC-6 cells and freshly isolated mouse and human primary pancreatic beta cells as models. The results showed biotin uptake by pancreatic beta-TC-6 cells occurs via a Na(+)-dependent, carrier-mediated process, that is sensitive to desthiobiotin, as well as to pantothenic acid and lipoate; the process is also saturable as a function of concentration (apparent Km = 22.24 ± 5.5 μM). These cells express the sodium-dependent multivitamin transporter (SMVT), whose knockdown (with doxycycline-inducible shRNA) led to a sever inhibition in biotin uptake. Similarly, uptake of biotin by mouse and human primary pancreatic islets is Na(+)-dependent and carrier-mediated, and both cell types express SMVT. Biotin uptake by pancreatic beta-TC-6 cells is also adaptively regulated (via transcriptional mechanism) by extracellular substrate level. Chronic treatment of pancreatic beta-TC-6 cells with bacterial lipopolysaccharides (LPS) leads to inhibition in biotin uptake. This inhibition is mediated via a Toll-Like receptor 4-mediated process and involves a decrease in membrane expression of SMVT. These findings show, for the first time, that pancreatic beta cells/islets take up biotin via a specific and regulated carrier-mediated process, and that the process is sensitive to the effect of LPS.
authors.affiliation: Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; and Department of Veterans Affairs Medical Center, Long Beach, California.
authors.forename: Abhisek
authors.initials: A
authors.lastname: Ghosal
authors.affiliation: Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; and Department of Veterans Affairs Medical Center, Long Beach, California.
authors.forename: Thillai V
authors.initials: TV
authors.lastname: Sekar
authors.affiliation: Departments of Medicine and Physiology/Biophysics, University of California, Irvine, California; and Department of Veterans Affairs Medical Center, Long Beach, California hmsaid@uci.edu.
authors.forename: Hamid M
authors.initials: HM
authors.lastname: Said
mesh_terms: D000818:Animals; D001692:Biological Transport; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D010205:Pantothenic Acid / Q000494:pharmacology; D034622:RNA Interference; D027981:Symporters / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014162:Transfection
chemical_list: D008070:Lipopolysaccharides; D027981:Symporters; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C119981:biotin transporter; D010205:Pantothenic Acid; D001710:Biotin; C004749:desthiobiotin; D008063:Thioctic Acid
keywords: biotin; biotin uptake mechanism; pancreatic beta cells; transport regulation