Role of Vitamin D and Metformine on Pancreatic Tissue in an Experimental Model of Type II Diabetes Mellitus
Background: The study was done to evaluate the role of Vitamin D (Vit D) in an experimental model of type II DM and compare its effects with oral hypoglycemic drugs (Metformine).
Methods: 30 male rats were divided; control group, Diabetic group via administration of high fat diet then injection of streptozotocin . Diabetic rats were then divided into Diabetic group, Diabetic + Metformine group(n=6), Diabetic +Vit D (n=6), Diabetic + Metformine +Vit D (n=6). Fasting glucose, insulin, HOMA IR, Cholesterol, Triglycerides, C-Reactive protein (CRP), Glucagon like peptide (GLP1), Cyclooxygenase 2 (COX2) and Superoxide dismutase (SOD) were measured, Real time PCR for pancreatic expression levels of Caspase 3, IKKβ and Western plot of Pancreatic protein kinase beta (Akt) and INGAP (islet neogensis associated protein), and histopathological, immunohistochemical for pancreatic tissue.
Results: Increased glucose, fasting insulin, HOMA IR , cholesterol, triglycerides, CRP, COX2 and expression of levels of Caspase 3 and IK Kinase B and Akt in diabetic group in comparison to control. On the other hand, significant decreased levels of GLP1, SOD and INGAP in diabetic in comparison to control. On treatment with metformine or Vitamin D improved all parameters. In combined metformine and vitamin D therapy there was much improvement with no significant change from control.
Conclusions: Vitamin D and metformine improved inflammatory, oxidative stress, apoptotic conditions in an experimental model of type II DM and combined therapy causes more improvement, so it is better to give combined therapy.
2- Maedler K, Oberholzer J, Bucher P, Spinas GA, Donath MY. Monounsaturated fatty acids prevent the deleterious effects of palmitate and high glucose on human pancreatic beta-cell turnover and function. Diabetes. 2003; 52 :726 –733.
3- Donath MY Targeting inflammation in the treatment of type 2 diabetes. Diabetes Obes Metab. 2013; 15:193–196
4- Häcker H, Karin M. Regulation and function of IKK and IKK-related kinases. Sci. STKE .2006; 357: re13
5- Karin M. How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex.Oncogene . 1999; 18:6867–74.
6- Haligur M, Topsakal S, and Ozmen O. Early Degenerative Effects of Diabetes Mellitus on Pancreas, Liver, and Kidney in Rats: An Immunohistochemical Study Experimental Diabetes Research 2012 : Article ID 120645, 10 pages.
7- Pittenger GL, Taylor-Fishwick DA, Johns RH, Burcus N, Kosuri S, Vinik AI.Intramuscular injection of islet neogenesisassociated protein peptide stimulates pancreatic islet neogenesis in healthy dogs. Pancreas. 2007; 34:103
8- Guo S, Dai C, Guo M, et al. Inactivation of specific β cell transcription factors in type 2 diabetes. J Clin Invest 2013; 123:3305–3316.
9- Woodgett J.R. Recent advances in the protein kinase B signaling pathway. Curr Opin Cell Biol. 2005; 17: 150-157
10- Marzban L and Park K Verchere CB. Islet amyloid polypeptide and type 2 diabetes. Exp Gerontol. 2003; 38:347-51.
11- Chagas C. E. A., Borges M. C., Martini L. A., and Rogero M. MFocus on vitamin D, inflammation and type 2 diabetes. Nutrients. 2012; 4 :52–67
12- Skibicka KP. The central GLP-1: implications for food and drug reward. Front Neurosci. 2013; 7: 181
13- Srinivasan K, Patole PS, Kaul CL, Ramarao P. Reversal of glucose intolerance by by pioglitazone in high fat diet-fed rats. Methods Find Exp Clin Pharmacol. 2004; 5:327-33.
14- Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao PCombination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005; 4:313-20.
15- Tan Z, Xu Z, Gui Q, Wu W, Yang Y. Gliquidone versus metformin: differential effects on aorta in streptozotocin induced diabetic rats. Chin Med J (Engl). 2014; 127:1298-303.
16- Lokeshwar BL, Schwartz GG, Selzer MG, Burnstein KL, Zhuang SH, Block NL, Binderup L. Inhibition of prostate cancer metastasis in vivo: a comparison of 1,23-dihydroxyvitamin D (calcitriol) and EB1089. Cancer Epidemiol Biomarkers Prev.1999;3:241-8.
17- Osanai K, Higuchi J, Oikawa R, Kobayashi M, Tsuchihara K, Iguchi M, Huang J, Voelker D R, Toga H. Altered lung surfactant system in a Rab38-deficient rat model of Hermansky-Pudlak syndrome. Am J Physiol Lung Cell Mol Physiol .2010;298: L243–251.
18- Nauck M, Graziani MS, Jarausch J, Bruton D, Cobbaert C, Cole TG, Colella F, Lefevre F, Gillery P, Haas B, Law T, König M, Macke M, März W, Meier C, Riesen W, van Vliet M, Wieland H, Rifai NA new liquid homogeneous assay for HDL cholesterol determination evaluated in seven laboratories in Europe and the United States. Clin Chem Lab Med.1999; 37(11-12):1067-76.
19- Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry. 1972; 18: (6): 499-502.
20- Delams H. G. Biochemical analysis of human and animal serum for monoclonal antibodies using ELISA. Biochem. 1986; 14, 214–231.
21- Mathews DR., Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia.1985: 28: 412–419
22- Kiernan JA Histological and Histochemical methods: Theory and Practice, third edition, Arnold publisher, London, New York and New Delhi: 2001; 111-162.
23- Herndon A. M. Breshears M. A., McFarlane D. Oxidative Modification, Inflammation and Amyloid in the Normal and Diabetic Cat Pancreas. J. Comp. Path. 2014;151:352-362
24- Emsley R, Dunn G, White IR Mediation and moderation of treatment effects in randomized controlled trials of complex interventions. Stat Methods Med Res 2010;19: 237-70.
25- Zhou R., Tardivel A., Thorens B., Choi I. Tschopp, J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nature Immunol. 2010; 11: 136–140.
26- Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S, Ray S, Majumdar SS, Bhattacharya S. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nature Med. 2012;18:1279–1285
27- Brownlee M. The pathobiology of diabetic complications. Diabetes 2005;54:1615
28- Hussain AR, Ahmed M, Al-Jomah NA, Khan AS, Manogaran P, Sultana M, Abubaker J, et al. Curcumin suppresses constitutive activation of nuclear factor-kappa B and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines. Mol Cancer Ther. 2008; 7:3318-29.
29- Liu HY, Yehuda-Shnaidman E, Hong T, Han J, Pi J, Liu Z, Cao W. Prolonged exposure to insulin suppresses mitochondrial production in primary hepatocytes. J Biol Chem 2009; 284:14087-95
30- Wang Y, Chang J, Li YC, Li YS, Shyy JY, Chien S. Shear stress and VEGF activate IKK via the Flk-1/Cbl/Akt signaling pathway. Am J Physiol Heart Circ Physiol. 2004; 286: 685-692.
31- Lim GE, Brubaker PL. The effect of insulin resistance on glucagon-like peptide-1 (GLP-1) secretion in mouse enteroendocrine L cells. Diabetes 2006;55 (Suppl. 1):A85
32- Akbarzadeh A., Norouzian, A.D., Mehrabi, M.R., Jamshidi,S.H., Farhangi, A., Allah, V.A., Mofidian S.M.A., Lame R.B Induction of diabetes by streptozotocin in rats. Indian journal of clinical biochemistry. 2007;22:60-64.
33- Herndon A.M., Breshears M.A., McFarlane D. Oxidative Modification, Inflammation and Amyloid in the Normal and Diabetic Cat Pancreas. Journal of Comparative Pathology. 2014; 151(4) :352–362
34- Chen K. Athero-protective actions of two oral antidiabetic drugs: Suppression of inflammation and oxidative stress. J Cardiovasc Dis Res. 2012;3:3
35- Marchetti P, Del Guerra S, Marselli L, Lupi R, Masini M, Pollera M, Bugliani M, Boggi U, Vistoli F, Mosca F, Del Prato S. Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J Clin Endocrinol Metab. 2004; 89 :5535-41.
36- Isoda K, Young J, Zirlik AMetformin inhibits Proinflammatory Responses and Nuclear Factor ĸß in Human Vascular Wall Cells. Arterioscler Thromb Vasc Biol. 2006; 26:611–617.
37- Mannucci E, Tesi F, Bardini G, Ognibene A, Petracca MG, Ciani S, Pezzatini A, Brogi M, Dicembrini I, Cremasco F, Messeri G, Rotella CM. Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes. Diabetes Nutr Metab. 2004; 17(6):336-42.
38- Krishnan AV, Feldman D. Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol Toxicol. 2011;51:311-36.
39- Chen Y, Zhang J, Ge X, Du J, Deb DK, Li YC. Vitamin D receptor inhibits nuclear factor κB activation by interacting with IκB kinase β protein. J Biol Chem. 2013; 288:19450-8.
40- Wang Q, He Y, Shen Y , Qianqian Z , Chen D, Zuo C, Qin J , Wang H, Wang J and Yu Y. Vitamin D Inhibits COX-2 Expression and Inflammatory Response by Targeting Thioesterase Superfamily Member 4. J Biol Chem. 2014; 289: 11681–11694
Copyright (c) 2016 International Archives of BioMedical and Clinical Research
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.