The Library
Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes
Tools
Tools
Tools
Larkin, James Robert, Zhang, F. (Fang), Godfrey, L. (Lisa), Molostvov, Guerman, Zehnder, Daniel, Rabbani, Naila and Thornalley, Paul J. (2012) Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes. PLoS One, Vol.7 (No.12). Article no. e53175. doi:10.1371/journal.pone.0053175 ISSN 1932-6203.
|
Text
WRAP_Larkin_journal.pone.0053175.pdf - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (531Kb) | Preview |
Official URL: http://dx.doi.org/10.1371/journal.pone.0053175
Abstract
Increased renal clearance of thiamine (vitamin B1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: −76% and −53% respectively, p<0.001; transporter protein −77% and −83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
||||
| Library of Congress Subject Headings (LCSH): | Vitamin B1 deficiency, Vitamin B1 -- Physiological transport, Diabetes, Diabetic nephropathies, Glucose | ||||
| Journal or Publication Title: | PLoS One | ||||
| Publisher: | Public Library of Science | ||||
| ISSN: | 1932-6203 | ||||
| Official Date: | 2012 | ||||
| Dates: |
|
||||
| Volume: | Vol.7 | ||||
| Number: | No.12 | ||||
| Page Range: | Article no. e53175 | ||||
| DOI: | 10.1371/journal.pone.0053175 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Date of first compliant deposit: | 1 August 2016 | ||||
| Date of first compliant Open Access: | 1 August 2016 | ||||
| Funder: | Diabetes UK |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
