Abstract
Thiamine helps transketolase in removing toxic metabolites, counteracting high glucose-induced damage in microvascular cells, and progression of diabetic retinopathy/nephropathy in diabetic animals. Diabetic subjects show reduced thiamine levels. Hyperglycemia and reduced thiamine availability concur in impairing thiamine transport inside the blood-retinal barrier, with thiamine transporter-2 (THTR2) primarily involved. Here, we examined the behavior of thiamine transporter-1 (THTR1), THTR2, and their transcription factor Sp1 in response to high glucose and altered thiamine availability in renal cells involved in diabetic nephropathy. Human proximal tubule epithelial cells, podocytes, glomerular endothelial, and mesangial cells were exposed to high glucose and/or thiamine deficiency/oversupplementation. Localization and modulation of THTR1, THTR2, and Sp1; intracellular thiamine; transketolase activity; and permeability to thiamine were examined. Reduced thiamine availability and hyperglycemia impaired thiamine transport and THTR2/Sp1 expression. Intracellular thiamine, transketolase activity, and permeability were strongly dependent on thiamine concentrations and, partly, excess glucose. Glomerular endothelial cells were the most affected by the microenvironmental conditions. Our results confirmed the primary role of THTR2 in altered thiamine transport in cells involved in diabetic microvascular complications. Lack of thiamine concurs with hyperglycemia in impairing thiamine transport. Thiamine supplementation could represent a therapeutic option to prevent or slow the progression of these complications.
Highlights
Introduction published maps and institutional affilThe microvascular complications of diabetes are a primary cause of renal failure, blindness, and limb amputation in industrialized countries
Our findings suggest that reduced thiamine availability concurs with hyperglycemia to impair thiamine transport into cells involved in diabetic nephropathy (DN), with thiamine transporter-2 (THTR2) primarily involved
Our results showed that thiamine transporter-1 (THTR1) was slightly influenced by glucose variations in either model, while THTR2 and Sp1 expression increased in HGEC and, partly, in HMC, under high/intermittent glucose conditions, probably as a consequence of the increased need of thiamine inside the cells to deal with the excess glucose concentrations and accelerated glycolytic flux
Summary
The microvascular complications of diabetes are a primary cause of renal failure, blindness, and limb amputation in industrialized countries. Their development has always been considered as strictly related to glycemic fluctuations and diabetes duration [1], a percentage of patients does not develop these complications despite poor glycemic control, while others, better controlled as regards glycated hemoglobin and blood pressure, are highly susceptible to them [2], suggesting the influence of other variables. Thiamine was shown to reduce reactive oxygen species (ROS) production in microvascular cells grown in diabetic-like conditions and in diabetic animals [6,7]. In vivo studies on animals with experimental diabetes showed iations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
