J 2018

Transketolase Activity but not Thiamine Membrane Transport Change in Response to Hyperglycaemia and Kidney Dysfunction

CHALÁSOVÁ, Katarína, Lukáš PÁCAL, Anna PLESKAČOVÁ, Lucia KNOPFOVÁ, Jitka ŘEHOŘOVÁ et. al.

Základní údaje

Originální název

Transketolase Activity but not Thiamine Membrane Transport Change in Response to Hyperglycaemia and Kidney Dysfunction

Autoři

CHALÁSOVÁ, Katarína (703 Slovensko, domácí), Lukáš PÁCAL (203 Česká republika, garant, domácí), Anna PLESKAČOVÁ (203 Česká republika, domácí), Lucia KNOPFOVÁ (203 Česká republika, domácí), Jitka ŘEHOŘOVÁ (203 Česká republika), Marie TOMANDLOVÁ (203 Česká republika, domácí), Josef TOMANDL (203 Česká republika, domácí) a Kateřina KAŇKOVÁ (203 Česká republika, domácí)

Vydání

EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, STUTTGART, JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH, 2018, 0947-7349

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30202 Endocrinology and metabolism

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 1.927

Kód RIV

RIV/00216224:14110/18:00106913

Organizační jednotka

Lékařská fakulta

UT WoS

000430440200008

Klíčová slova anglicky

Thiamine; transketolase; pentose phosphate pathway; diabetes; chronic kidney disease; diabetic nephropathy

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 26. 3. 2019 10:32, Soňa Böhmová

Anotace

V originále

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 < 0.05) in vitro. Analysis of blood samples from CKD patients with and without diabetes and from controls did not reveal any difference in gene expression and protein levels of thiamine transporters while TKT activity and TDP in erythrocytes gradually increased with decreasing kidney function being highest in patients with CKD3-4 of both diabetic and non-diabetic aetiology. Hyperglycaemia and uremic serum mimicking CKD in diabetes did not affect TKT activity in vitro (P < 0.05). 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.

Návaznosti

NV16-28040A, projekt VaV
Název: Dlouhodobé dopady gestačního diabetes mellitus pro metabolické zdraví žen časně postpartum: význam nových diagnostických kritérií