Tag Archives: experimental type 1 diabetes
Vitamin D(3) regulates hepatic VEGF-A and apelin expression in experimental type 1 diabetes
D. O. Labudzynskyi1*, I. O. Shymanskyi1, O. O. Lisakovska1,
A. O. Mazanova1, L. V. Natrus2, M. M. Veliky1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Bogomolets National Medical University, Kyiv, Ukraine;
*e-mail: konsument3@gmail.com
Received: 09 July 2019; Accepted: 15 May 2020
The deficiency of vitamin D is associated with the risk of various chronic diseases, including diabetes mellitus and its complications. Given the strong genomic action of vitamin D hormone-active form, its deficiency can lead to dysfunction of cytokine signaling pathways, including those dependent on vascular endothelial growth factors (VEGFs) and apelin. The present study was carried out to define the link between VEGF-A and apelin expression in liver, hepatocytes viability and vitamin D status at experimental type 1 diabetes in mice. We established that chronic hyperglycemia at streptozotocin-induced diabetes was accompanied by a 2.2-fold decrease in 25OHD content in the serum and increased hepatocytes apoptosis and necrosis. Vitamin D deficiency correlated with increased apelin and VEGF-A (8- and 1.6-fold respectively) expression. Almost complete restoration of circulatory 25OHD content in serum was achieved at vitamin D3 treatment (800 IU/kg, per os, for 2 months) followed by reduced apelin and VEGF-A expression in liver and the decline of hepatocytes apoptosis. We conclude that vitamin D3 can be involved in cell survival, angiogenesis and fibrogenesis by modulating VEGF-A and apelin dependent regulatory systems in diabetic liver.
Osteoprotective effects of vitamin D(3) in diabetic mice is VDR-mediated and regulated via RANKL/RANK/OPG axis
D. O. Labudzynskyi, І. О. Shymanskyi, O. O. Lisakovska, М. М. Veliky
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: konsumemt3@gmail.com
There is growing evidence that vitamin D3 deficiency could be a contributing factor in the development of different chronic diseases and their complications. A better understanding of how diabetes influences bone tissue metabolism may become an underlying basis for effective prevention and treatment of skeletal disorders in diabetes. This study was performed to define diabetes-associated impairments in bone tissue remodeling in relation to vitamin D bioavailability and to estimate the effects of cholecalciferol treatment. We established that chronic hyperglycemia in diabetes was accompanied by a 2.15-fold decrease of 25OHD content in the serum. Vitamin D deficiency correlated with impairments of tibia biomechanical properties (decline of bone maximal load and stiffness values). µCT analysis of tibia showed respectively 3.0-, 2.1- and 1.3-fold decreases in trabecular bone volume per tissue volume, trabecular number and cortical thickness in diabetes indicating the development of secondary osteoporosis. Diabetes led to up-regulation of NF-κB/phosho-p65, RANKL, RANK (2.3-, 1.51-, 1.72-fold respectively) and down-regulation of OC, OPG and VDR (1.5-, 1.6- and 1.8-fold respectively) in tibial tissue of diabetic mice. Diabetes-associated abnormalities in the serum levels of RANKL, OPG and TRAP were also detected. Restoration of circulatory 25OHD content was achieved due to cholecalciferol treatment. Better vitamin D availability and increased VDR expression resulted in normalization of RANKL/RANK/OPG- and NF-κB-associated pathways that attenuated diabetes-induced structural and biomechanical abnormalities in bone tissue.
Vitamin D(3) contribution to the regulation of oxidative metabolism in the liver of diabetic mice
D. O. Labudzynskyi, O. V. Zaitseva, N. V. Latyshko,
O. O. Gudkova, M. M. Veliky
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: konsumemt3@gmail.com
This work is devoted to the study of the features of oxidative metabolism of hepatocytes in diabetic mice and those under the vitamin D3 action. We found out that a 2.5-fold decrease of 25OHD3 content in the serum was caused by chronic hyperglycemia in diabetes. Intensification of the reactive oxygen species (ROS) and nitrogen monoxide (NO) production, protein oxidative modifications (detected by the contents of carbonyl groups and 3-nitrotyrosine), accumulation of diene conjugates and TBA-reactive products of lipid peroxidation, and the decreased level of free SH-groups of low molecular weight compounds in the liver were accompanied by development of vitamin D3 deficient state. It was shown that there was a decrease in the key antioxidant enzymes activity (catalase, SOD), while the activity of prooxidant enzymes NAD(P)H:quinone oxidoreductase, xanthine oxidase and NAD(P)H oxidase was increased. The identified oxidative metabolism lesions caused the elevation of the hepatocytes necrotic death that was tested for the ability of their nuclei to accumulate propidium iodide. Prolonged vitamin D3 administration (during 2 months) at a dose of 20 IU to diabetic mice helps to reduce the ROS formation and biomacromolecules oxidative damage, normalizes the antioxidant system state in the liver and increases survival of hepatocytes. The results suggest that vitamin D3 is a key player in the regulation of the oxidative metabolism in diabetes.
Vitamin D(3) availability and functional activity of peripheral blood phagocytes in experimental type 1 diabetes
D. О. Labudzynskyi, І. О. Shymanskyy, V. М. Riasnyi, М. М. Veliky
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: konsument3@gmail.com
The study was devoted to identifying the relation between vitamin D3 availability (assessed by the level of circulatory 25OHD3), content of vitamin D3 25-hydroxylase isozymes CYP27A1 and CYP2R1 in hepatic tissue and functional activity of peripheral blood phagocytes in mice with experimental type 1 diabetes. It has been shown that diabetes is accompanied by the development of vitamin D3-deficiency which is characterized by decreased 25OHD3 content in blood serum and determined by changes in tissue expression of the major isoforms of vitamin D3 25-hydroxylase. The level of hepatic CYP27A1 was revealed to be markedly reduced with a concurrent significant augmentation of CYP2R1. Cholecalciferol administration resulted in normalization of tissue levels of both isoforms of vitamin D3 25-hydroxylase and blood serum 25OHD3 content. Diabetes-associated vitamin D3 deficiency correlated with a decrease in phagocytic activity of granulocytes and monocytes, and their ability to produce antibacterial biooxidants such as reactive oxygen and nitrogen forms. Vitamin D3 efficacy to attenuate these abnormalities of immune function was established, indicating an important immunoregulatory role of cholecalciferol in the phagocytic mechanism of antigens elimination implemented by granulocytes and monocytes.