Patients with type 1 or type 2 diabetes had increased renal clearance and fractional excretion of thiamine compared to healthy people. Renal mishandling of thiamine (vitamin B 1) in diabetes has recently emerged as a factor linked to the development of diabetic nephropathy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. It was also supported by a grant from British Heart Foundation to NR and PJT supporting a postdoctoral fellowship to LG. JRL thanks the University of Warwick for a PhD studentship. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This study was funded by a grant from Diabetes UK to NR and PJT which provided a PhD studentship to FZ. Received: AugAccepted: NovemPublished: December 28, 2012Ĭopyright: © 2012 Larkin et al. Virginia Commonwealth University, United States of America (2012) Glucose-Induced Down Regulation of Thiamine Transporters in the Kidney Proximal Tubular Epithelium Produces Thiamine Insufficiency in Diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy.Ĭitation: Larkin JR, Zhang F, Godfrey L, Molostvov G, Zehnder D, Rabbani N, et al. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. 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. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. 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. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Increased renal clearance of thiamine (vitamin B 1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy.
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