Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Diabetic Hemodialysis: Vitamin D Supplementation and its Related Signaling Pathways Involved in Insulin and Lipid Metabolism

Author(s): Elahe S. Hosseini, Hamed H. Kashani, Hossein Nikzad, Alireza Soleimani, Hamed Mirzaei, Mohammd R. Tamadon and Zatollah Asemi*

Volume 19, Issue 8, 2019

Page: [570 - 578] Pages: 9

DOI: 10.2174/1566524019666190618144712

Price: $65

Abstract

Background: This study was conducted to determine the effects of vitamin D supplementation on some of the gene expressions related to insulin and lipid metabolism in diabetic hemodialysis (HD) patients.

Methods: A double-blind, randomized, placebo-controlled clinical trial was carried out in 55 patients with diabetic HD. The current project used two groups in which each subject received vitamin D supplements (50,000 IU, n=28) or placebo (50,000 IU, n=27) every 2 weeks for 12 weeks. Gene expression analyses (RT-PCR) were included to obtain the rate of gene expression of the related insulin and lipid metabolism genes in peripheral blood mononuclear cells (PBMCs) of patients with diabetic HD.

Results: Our data revealed that consumption of vitamin D supplementation enables to overexpress the peroxisome proliferation-activated receptor gamma (PPAR-γ) (P=0.001), AKT (P=0.04), PI3K (P=0.02), insulin receptor substrate-1 (IRS1) (P0.008) and glucose transporter type 4 (GLUT-4) (P=0.01) and downregulate the expression of protein kinase C (PKC) (P=0.001) in patients with diabetic HD than control group following the 12-week intervention. In addition, vitamin D supplementation downregulated low-density lipoprotein receptor (LDLR) (P=0.03) expression in the subjects with diabetic HD than the control group. Vitamin D supplementation did not show any effects on the expression of pyruvate dehydrogenase kinase 1 (PDK1) (P=0.37), IRS2 (P=0.90) and lipoprotein (a) [Lp(a)] (P=0.05).

Conclusion: Our findings confirmed that diabetic HD subjects who received the vitamin D supplementation (for 12 weeks), showed a significant overexpression in the PPAR-γ, AKT, PI3K, IRS1 and GLUT4 genes, and also showed a significant downregulation in the PKC and LDLR genes. Moreover, no effects on PDK1, IRS2 and Lp(a) expression were observed.

Keywords: Vitamin D supplementation, hemodialysis, signaling pathway, insulin, lipid, metabolism.

[1]
Zoccali C, Tripepi G, Cambareri F, et al. Adipose tissue cytokines, insulin sensitivity, inflammation, and cardiovascular outcomes in end-stage renal disease patients. J Ren Nutr 2005; 15(1): 125-30.
[http://dx.doi.org/10.1053/j.jrn.2004.09.036] [PMID: 15648021]
[2]
Hung AM, Ikizler TA. Factors determining insulin resistance in chronic hemodialysis patients. Contrib Nephrol 2011; 171: 127-34.
[http://dx.doi.org/10.1159/000327177] [PMID: 21625101]
[3]
Rhee CM, Leung AM, Kovesdy CP, Lynch KE, Brent GA, Kalantar-Zadeh K. Updates on the management of diabetes in dialysis patients. Semin Dial 2014; 27(2): 135-45.
[http://dx.doi.org/10.1111/sdi.12198] [PMID: 24588802]
[4]
Reis A, Rudnitskaya A, Chariyavilaskul P, et al. Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease. J Lipid Res 2015; 56(2): 413-22.
[http://dx.doi.org/10.1194/jlr.M055624] [PMID: 25424003]
[5]
Su H, Wan C, Lei CT, et al. Lipid Deposition in kidney diseases: Interplay among redox, lipid mediators, and renal impairment. Antioxid Redox Signal 2017.
[http://dx.doi.org/10.1089/ars.2017.7066] [PMID: 28325081]
[6]
de Boer IH. Vitamin D and glucose metabolism in chronic kidney disease. Curr Opin Nephrol Hypertens 2008; 17(6): 566-72.
[http://dx.doi.org/10.1097/MNH.0b013e32830fe377] [PMID: 18941348]
[7]
Cupisti A, Vigo V, Baronti ME, D’Alessandro C, Ghiadoni L, Egidi MF. Vitamin D status and cholecalciferol supplementation in chronic kidney disease patients: An Italian cohort report. Int J Nephrol Renovasc Dis 2015; 8: 151-7.
[http://dx.doi.org/10.2147/IJNRD.S90968] [PMID: 26640388]
[8]
Haddad Kashani H, Seyed Hosseini E, Nikzad H, et al. The effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis: A randomized, double-blind, placebo-controlled trial. Front Pharmacol 2018; 9: 50.
[http://dx.doi.org/10.3389/fphar.2018.00050] [PMID: 29456507]
[9]
Ibrahim MA, Sarhan II, Halawa MR, et al. Study of the effect of vitamin D supplementation on glycemic control in type 2 diabetic prevalent hemodialysis patients. Hemodial Int 2015; 19(Suppl. 3): S11-9.
[http://dx.doi.org/10.1111/hdi.12347] [PMID: 26448381]
[10]
Hoseini R, Damirchi A, Babaei P. Vitamin D increases PPARγ expression and promotes beneficial effects of physical activity in metabolic syndrome. Nutrition 2017; 36: 54-9.
[http://dx.doi.org/10.1016/j.nut.2016.06.010] [PMID: 28336108]
[11]
Boon N, Hul GB, Sicard A, et al. The effects of increasing serum calcitriol on energy and fat metabolism and gene expression. Obesity (Silver Spring) 2006; 14(10): 1739-46.
[http://dx.doi.org/10.1038/oby.2006.200] [PMID: 17062803]
[12]
Baldassare JJ, Bi Y, Bellone CJ. The role of p38 mitogen-activated protein kinase in IL-1 beta transcription. J Immunol 1999; 162(9): 5367-73.
[PMID: 10228013]
[13]
Pisprasert V, Ingram KH, Lopez-Davila MF, Munoz AJ, Garvey WT. Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans. Diabetes Care 2013; 36(4): 845-53.
[http://dx.doi.org/10.2337/dc12-0840] [PMID: 23223406]
[14]
Dunkley PR, Jarvie PE, Robinson PJ. A rapid Percoll gradient procedure for preparation of synaptosomes. Nat Protoc 2008; 3(11): 1718-28.
[http://dx.doi.org/10.1038/nprot.2008.171] [PMID: 18927557]
[15]
Kotur-Stevuljevic J, Simic-Ogrizovic S, Dopsaj V, et al. A hazardous link between malnutrition, inflammation and oxidative stress in renal patients. Clin Biochem 2012; 45(15): 1202-5.
[http://dx.doi.org/10.1016/j.clinbiochem.2012.04.021] [PMID: 22580395]
[16]
Dastorani M, Aghadavod E, Mirhosseini N, et al. The effects of vitamin D supplementation on metabolic profiles and gene expression of insulin and lipid metabolism in infertile polycystic ovary syndrome candidates for in vitro fertilization. Reprod Biol Endocrinol 2018; 16(1): 94.
[http://dx.doi.org/10.1186/s12958-018-0413-3] [PMID: 30286768]
[17]
Manna P, Achari AE, Jain SK. Vitamin D supplementation inhibits oxidative stress and upregulate SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in adipose tissue of high fat diet-fed diabetic mice. Arch Biochem Biophys 2017; 615: 22-34.
[http://dx.doi.org/10.1016/j.abb.2017.01.002] [PMID: 28063949]
[18]
Manna P, Jain SK. Vitamin D up-regulates glucose transporter 4 (GLUT4) translocation and glucose utilization mediated by cystathionine-γ-lyase (CSE) activation and H2S formation in 3T3L1 adipocytes. J Biol Chem 2012; 287(50): 42324-32.
[http://dx.doi.org/10.1074/jbc.M112.407833] [PMID: 23074218]
[19]
Manna P, Achari AE, Jain SK. 1,25(OH)2-vitamin D3 upregulates glucose uptake mediated by SIRT1/IRS1/GLUT4 signaling cascade in C2C12 myotubes. Mol Cell Biochem 2018; 444(1-2): 103-8.
[http://dx.doi.org/10.1007/s11010-017-3235-2] [PMID: 29188534]
[20]
Huang S, Czech MP. The GLUT4 glucose transporter. Cell Metab 2007; 5(4): 237-52.
[http://dx.doi.org/10.1016/j.cmet.2007.03.006] [PMID: 17403369]
[21]
Stenbit AE, Tsao TS, Li J, et al. GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat Med 1997; 3(10): 1096-101.
[http://dx.doi.org/10.1038/nm1097-1096] [PMID: 9334720]
[22]
Aljabri KS, Bokhari SA, Khan MJ. Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency. Ann Saudi Med 2010; 30(6): 454-8.
[http://dx.doi.org/10.4103/0256-4947.72265] [PMID: 21060157]
[23]
Wallberg-Henriksson H, Zierath JR. GLUT4: a key player regulating glucose homeostasis? Insights from transgenic and knockout mice. (review). Mol Membr Biol 2001; 18(3): 205-11. [review].
[http://dx.doi.org/10.1080/09687680110072131] [PMID: 11681787]
[24]
Chang L, Chiang SH, Saltiel AR. Insulin signaling and the regulation of glucose transport. Mol Med 2004; 10(7-12): 65-71.
[http://dx.doi.org/10.2119/2005-00029.Saltiel] [PMID: 16307172]
[25]
Fouque D, Kalantar-Zadeh K, Kopple J, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int 2008; 73(4): 391-8.
[http://dx.doi.org/10.1038/sj.ki.5002585] [PMID: 18094682]
[26]
Shinohara K, Shoji T, Emoto M, et al. Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease. J Am Soc Nephrol 2002; 13(7): 1894-900.
[http://dx.doi.org/10.1097/01.ASN.0000019900.87535.43] [PMID: 12089386]
[27]
Kayaniyil S, Vieth R, Retnakaran R, et al. Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes. Diabetes Care 2010; 33(6): 1379-81.
[http://dx.doi.org/10.2337/dc09-2321] [PMID: 20215450]
[28]
Rosen CJ, Adams JS, Bikle DD, et al. The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. Endocr Rev 2012; 33(3): 456-92.
[http://dx.doi.org/10.1210/er.2012-1000] [PMID: 22596255]
[29]
Kato S. The function of vitamin D receptor in vitamin D action. J Biochem 2000; 127(5): 717-22.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a022662] [PMID: 10788778]
[30]
Bakhshalizadeh S, Amidi F, Shirazi R, Shabani Nashtaei M. Vitamin D3 regulates steroidogenesis in granulosa cells through AMP-activated protein kinase (AMPK) activation in a mouse model of polycystic ovary syndrome. Cell Biochem Funct 2018; 36(4): 183-93.
[http://dx.doi.org/10.1002/cbf.3330] [PMID: 29676471]
[31]
Riek AE, Oh J, Darwech I, et al. Vitamin D3 supplementation decreases a unique circulating monocyte cholesterol pool in patients with type 2 diabetes. J Steroid Biochem Mol Biol 2018; 177: 187-92.
[http://dx.doi.org/10.1016/j.jsbmb.2017.09.011] [PMID: 28941998]
[32]
Oh J, Weng S, Felton SK, et al. 1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation 2009; 120(8): 687-98.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.856070] [PMID: 19667238]
[33]
Riek AE, Oh J, Bernal-Mizrachi C. 1,25(OH)2 vitamin D suppresses macrophage migration and reverses atherogenic cholesterol metabolism in type 2 diabetic patients. J Steroid Biochem Mol Biol 2013; 136: 309-12.
[http://dx.doi.org/10.1016/j.jsbmb.2012.12.019] [PMID: 23333932]
[34]
Aypak C, Türedi O, Yüce A. The association of vitamin D status with cardiometabolic risk factors, obesity and puberty in children. Eur J Pediatr 2014; 173(3): 367-73.
[http://dx.doi.org/10.1007/s00431-013-2177-2] [PMID: 24132388]
[35]
Li S, Chu Q, Ma J, et al. Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production? J Clin Endocrinol Metab 2017; 102(3): 810-21.
[PMID: 27886515]
[36]
Mikolasevic I, Žutelija M, Mavrinac V, Orlic L. Dyslipidemia in patients with chronic kidney disease: etiology and management. Int J Nephrol Renovasc Dis 2017; 10: 35-45.
[http://dx.doi.org/10.2147/IJNRD.S101808] [PMID: 28223836]
[37]
Chen SC, Tseng CH. Dyslipidemia, kidney disease, and cardiovascular disease in diabetic patients. Rev Diabet Stud 2013; 10(2-3): 88-100.
[http://dx.doi.org/10.1900/RDS.2013.10.88] [PMID: 24380085]
[38]
Wang H, Xia N, Yang Y, Peng DQ. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis 2012; 11: 42.
[http://dx.doi.org/10.1186/1476-511X-11-42] [PMID: 22433171]
[39]
Kaplan M, Kerry R, Aviram M, Hayek T. High glucose concentration increases macrophage cholesterol biosynthesis in diabetes through activation of the sterol regulatory element binding protein 1 (SREBP1): inhibitory effect of insulin. J Cardiovasc Pharmacol 2008; 52(4): 324-32.
[http://dx.doi.org/10.1097/FJC.0b013e3181879d98] [PMID: 18791464]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy