1,25-Dihydroxyvitamin D increases the gene expression of enzymes protecting from glucolipotoxicity in peripheral blood mononuclear cells and human primary endothelial cells

Abstract

Besides its classical function as an orchestrator of calcium and phosphorus homeostasis, vitamin D also affects insulin secretion and tissue efficiency. A number of studies have consistently reported the inverse relationship between vitamin D deficiency and type 2 diabetes. Activation of certain metabolic pathways and down-stream transcription factors may protect from glucolipotoxicity and their targeted activation -e.g. by vitamin D - might explain the detrimental role of vitamin D deficiency in diabetes. The aim of the study was to quantify gene and protein expression of selected enzymes involved in the protection from glucolipotoxicity, specifically glyoxalase 1 (GLO1), and other enzymes with antioxidant activity - hemoxygenase (HMOX), thiamin pyrophosphokinase (TPK1) and transketolase (TKT), under normo- and hyperglycemic conditions and upon addition of vitamin D in peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The results of our study indicate that the active form of vitamin D regulates gene expression of enzymes opposing the harmful effect of glucolipotoxicity whose activities appear to be suppressed by hyperglycemia. However, we were unable to confirm this effect on protein expression. While we cannot speculate on the effect of vitamin D on diabetes itself our results support its role in the protection against existing glucolipotoxicity therefore possibly translating into the prevention of development of diabetic complications.

Effects of vitamin D supplementation on advanced glycation end products signaling pathway in T2DM patients: a randomized, placebo-controlled, double blind clinical trial

“…With respect to previous studies, over expression of GLO1 can effectively reduce AGEs formation [35]. In this study, the GLO1 expression level in PBMCs of T2DM indicated no change after receiving vitamin D. Up to now; only one study has examined the vitamin D effect on GLO1 expression with conflicting results in different cells [13]. Therefore, further studies are required in this field.…”

“…Human glyoxalase I is a dimeric Zn (2+) metalloenzyme, and was expressed in different cell types like immune cells and endothelial cells. Glyoxalase-1 increased expression reduces the inflammatory and oxidative processes that were caused by AGEs [13, 14]. It has also been indicated that TNF-α is a RAGE gene expression regulator [15].…”

The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy

“…Vitamin D was also reported to exert a protective role against glycative stress [210,211]. Vitamin D supplementation in type-2 diabetes participants showed a trend in increasing GLO1 expression, a transcriptional downregulation of RAGE receptor and decreased in AGE serum in a double-blind randomized placebo-controlled [211].…”

Maternal asthma and gestational diabetes mellitus: Exploration of potential associations

“…61 It may also play a protective role against glucolipotoxicity, with one in vitro study supporting 1,25(OH)D in the regulation of key enzymes involved in protective pathways. 62 Given these findings, and the documented low 25(OH)D levels during pregnancy, it is plausible that the increased prevalence of GDM in asthma is mediated via lower 25(OH)D levels, reducing insulin secretion and, consequently, increasing blood glucose levels.…”

“…61 It may also play a protective role against glucolipotoxicity, with one in vitro study supporting 1,25(OH)D in the regulation of key enzymes involved in protective pathways. 62…”