Transketolase Activity but not Thiamine Membrane Transport Change in Response to Hyperglycaemia and Kidney Dysfunction
| Autor: | Kateřina Kaňková, Katarína Chalásová, Lucia Knopfová, Josef Tomandl, Lukáš Pácal, Jitka Řehořová, Marie Tomandlová, Anna Pleskačová |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Erythrocytes Endocrinology Diabetes and Metabolism Type 2 diabetes Biology Transketolase Diabetic nephropathy 03 medical and health sciences Endocrinology Diabetes mellitus Internal medicine Internal Medicine medicine Humans Diabetic Nephropathies Thiamine Renal Insufficiency Chronic Aged Biological Transport General Medicine Middle Aged medicine.disease 3. Good health 030104 developmental biology Diabetes Mellitus Type 2 Hyperglycemia Transketolase activity Female Thiamine transmembrane transport Kidney disease |
| Zdroj: | Experimental and clinical endocrinologydiabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 126(4) |
| ISSN: | 1439-3646 |
| Popis: | Aim Pentose phosphate pathway (PPP) with key enzyme transketolase (TKT), represents a potentially ‘protective’ mechanism in hyperglycaemia. Diabetic kidney disease (DKD), a common complication of both type 1 and type 2 diabetes associated with significant morbidity and mortality, represents the most common cause of chronic kidney disease (CKD). We hypothesized that protective PPP action in diabetes and eventually even more severely in concomitant DKD might be compromised by limited intracellular availability of an active TKT cofactor thiamine diphosphate (TDP). Methods Effect of hyperglycaemia on gene expression and protein levels of key PPP loci was studied in vitro using human cell lines relevant to diabetes (HUVEC and HRGEC) and (together with measurement of TKT activity, plasma thiamine and erythrocyte TDP concentration) in vivo in diabetic vs. non-diabetic subjects with comparable renal function (n=83 in total). Results Hyperglycaemia significantly decreased protein levels of RFC-1, THTR1, THTR2 and TKT (P Conclusion Both in vitro and human experiments showed decrease or unchanged expression, respectively, of thiamine transporters induced by hyperglycaemia while TKT activity in parallel with intracellular TDP was increased in CKD patients with or without diabetes. Therefore, lack of adaptive increase of thiamine transmembrane transport allowing further increase of TKT activity might contribute to compromised PPP function in diabetes and CKD and to the development of glycotoxic injury. |
| Databáze: | OpenAIRE |
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