L‐cysteine supplementation upregulates glutathione (GSH) and vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in liver, and increases blood levels of GSH, VDBP, and 25‐hydroxy‐vitamin D in Zucker diabetic fatty rats

Abstract

ScopeVitamin D binding protein (VDBP) status has an effect on and can potentially improve the status of 25(OH) vitamin D and increase the metabolic actions of 25(OH) vitamin D under physiological and pathological conditions. Diabetes is associated with lower levels of glutathione (GSH) and 25(OH) vitamin D. This study examined the hypothesis that upregulation of GSH will also upregulate blood levels of VDBP and 25(OH) vitamin D in type 2 diabetic rats.Methods and resultsL‐cysteine (LC) supplementation was used to upregulate GSH status in a FL83B hepatocyte cell culture model and in vivo using Zucker diabetic fatty (ZDF) rats. Results show that LC supplementation upregulates both protein and mRNA expression of VDBP and vitamin D receptor (VDR) and GSH status in hepatocytes exposed to high glucose, and that GSH deficiency, induced by glutamate cysteine ligase knockdown, resulted in the downregulation of GSH, VDBP, and VDR and an increase in oxidative stress levels in hepatocytes. In vivo, LC supplementation increased GSH and protein and mRNA expression of VDBP and vitamin D 25‐hydroxylase (CYP2R1) in the liver, and simultaneously resulted in elevated blood levels of LC and GSH, as well as increases in VDBP and 25(OH) vitamin D levels, and decreased inflammatory biomarkers in ZDF rats compared with those in placebo‐supplemented ZDF rats consuming a similar diet.ConclusionLC supplementation may provide a novel approach by which to raise blood levels of VDBP and 25(OH) vitamin D in type 2 diabetes.

Plasma VDBP, 25(OH)D, and GSH levels predict surgical outcome in patients with cervical spondylotic myelopathy

“…Logistic regression in our study revealed positive correlation among plasma VDBP, 25(OH)D, and GSH levels. Consistently, it has been pointed out that positive link between plasma levels of VDBP and 25(OH)D and those of GSH; specifically, lower plasma levels of VDBP and 25(OH)D correlated with lower GSH level, and increases in GSH level upregulated 25(OH)D and VDBP status in Zucker diabetic fatty rats . Supplementation of GSH could raise blood levels of VDBP and vitamin in African‐American patients with type 2 diabetes .…”

“…Consistently, it has been pointed out that positive link between plasma levels of VDBP and 25(OH)D and those of GSH; specifically, lower plasma levels of VDBP and 25(OH)D correlated with lower GSH level, and increases in GSH level upregulated 25(OH)D and VDBP status in Zucker diabetic fatty rats. 10 Supplementation of GSH could raise blood levels of VDBP and vitamin in African-American patients with type 2 diabetes. 12 Another study also suggested a significant positive correlation between GSH level and blood levels of L-cysteine (LC) and vitamin D in type 2 diabetic patients.…”

“…Vitamin D‐binding protein (VDBP), also known as group‐specific component, acts as different roles in metabolic and biological pathways, including regulation of bone development, delivering vitamin D metabolites, binding to fatty acids, and it also plays a special part in osteoclast differentiation . A vitamin D metabolite in the blood, 25‐hydroxyvitamin D [25(OH)D] is formed by hydroxylation of cholecalciferol through vitamin D 25‐hydroxylase (CYP2R1) in the liver and transported in the circulation bound to VDBP . Vitamin D levels in the body is highly connected to the concentration of 25(OH)D, so the best way to estimate Vitamin D level is to measure 25(OH)D .…”

“…9 A vitamin D metabolite in the blood, 25-hydroxyvitamin D [25(OH)D] is formed by hydroxylation of cholecalciferol through vitamin D 25-hydroxylase (CYP2R1) in the liver and transported in the circulation bound to VDBP. 10 Vitamin D levels in the body is highly connected to the concentration of 25(OH)D, so the best way to estimate Vitamin D level is to measure 25(OH)D. 11 A previous study has shown that blood levels of glutathione (GSH), a cofactor of multiple enzymes that helps to maintain normal cell functions, have a positive relationship with those of VDBP and 1,25 (OH) 2 D in the blood of African-American patients with type 2 diabetes. 12 It was also demonstrated that vitamin D could upregulate glutamate cysteine ligase and glutathione reductase and increase cellular GSH formation in cultured monocytes.…”

Матеріали Українсько-Білоруської Міжнародної Конференції «Дефіцит І Недостатність Вітаміну D В Клінічній Практиці» (20-21 Жовтня 2017 Року, М Чернігів, Україна)

“…Взаимодействие комплекса рецептора VDR и 1,25D с ядерным рецептором цисретиноевой кислоты и образование гетеродимера объясняет эффект на гены-мишени, участвующие в регуляции роста и дифференцировке клеток [1,2]. Важным эффектом витамина А является протекция токсичности витамина D за счет снижения экспрессии витамин-К-зависимых белков [1][2][3]. Эти и другие многочисленные данные положены в основу концепции «витамин D + 12 витаминов», предложенной В.Б.…”