J Clin Diagn Res. 2017 Jul;11(7):FC06-FC10. doi: 10.7860/JCDR/2017/28418.10193. Epub 2017 Jul 01.
Comparison of Pioglitazone and Metformin Efficacy against Glucocorticoid Induced Atherosclerosis and Hepatic Steatosis in Insulin Resistant Rats.
Journal of clinical and diagnostic research : JCDR
I M Nagendra Nayak, Koyagura Narendar, Patil Ashok M, M G Jamadar, V Hemanth Kumar
Affiliations
Affiliations
- Professor and Head, Department of Pharmacology, Mount Zion Medical College, Adoor, Kerala, India.
- Lecturer, Department of Pharmacology, Al-Ameen Medical College, Vijayapura, Karnataka, India.
- Professor and Head, Department of Pathology, Al-Ameen Medical College, Vijayapura, Karnataka, India.
- Professor and Head, Department of Pharmacology, Al-Ameen Medical College, Vijayapura, Karnataka, India.
PMID: 28892924
PMCID: PMC5583870 DOI: 10.7860/JCDR/2017/28418.10193
Abstract
INTRODUCTION: Insulin Resistance is a major cause of Atherosclerosis (AS) and Non Alcoholic Fatty Liver Disease (NAFLD). These lipid alterations in blood vessels and liver may progress to cardiovascular abnormalities and cirrhosis respectively. Drugs like pioglitazone (PIO) and metformin (MET) are effective insulin sensitizers used in T2DM. But their efficacy and tolerability needs to be compared in IR associated abnormalities.
AIM: To compare the efficacy of PIO and MET in glucocorticoid induced AS, Hepatic Steatosis (HS) and IR in albino rats.
MATERIALS AND METHODS: Male Wistar albino rats were randomized into four groups (n=6). Group 1 (Normal control) rats consumed 2% gum acacia orally for 12 days. Group 2 {dexamethasone (DEX) control} rats were administered 2% gum acacia orally for 12 days and DEX (8 mg/kg) intraperitoneally (i.p.) from 7th to 12th day during the study period. Group 3 and 4 (PIO and MET control) rats received oral administration of PIO (45 mg/kg) and MET (1000 mg/kg) for 12 days respectively. Both groups were treated with DEX (8 mg/kg/i.p.) from 7th to 12th day during the study period. On last day, fasting blood was collected and rats were sacrificed by cervical dislocation; aorta and liver tissues were isolated for the histopathological examination. Body weight, liver weight and liver volume were measured. Blood samples were processed for biochemical parameters. The data were analysed by One-way Analysis of variance (ANOVA) followed by Scheffe's multiple comparison post-hoc test. The statistical significance was assumed at p<0.05.
RESULTS: Our results established the possible role of DEX in the development of AS and HS. Histopathological examination of Group 2 rats treated with DEX showed a marked lipid accumulation in the aorta and liver. Administration of MET and PIO resulted in partial to complete restoration of DEX induced fatty changes in aorta and liver. Both drugs significantly (p<0.05) prevented the elevation of insulin, lipid, glucose levels, liver weight and liver volume in DEX treated rats. They had significantly (p<0.05) improved body weight and insulin sensitivity. However, PIO was highly significant (p<0.05) compared to MET in reducing DEX induced IR complications.
CONCLUSION: These findings suggest that PIO was more effective insulin sensitizer compared to MET in reducing AS, HS and IR induced by glucocorticoids.
Keywords: Dexamethasone; Dyslipidemia; Fatty changes; Insulin sensitizers
References
- Int J Prev Med. 2014 Aug;5(8):927-46 - PubMed
- J Lipid Res. 2009 Apr;50 Suppl:S74-9 - PubMed
- Eur J Endocrinol. 2002 Mar;146(3):419-29 - PubMed
- Clin Chem. 1999 Jun;45(6 Pt 1):838-46 - PubMed
- J Cardiovasc Pharmacol. 2005 Dec;46(6):773-8 - PubMed
- Clin Diabetes Endocrinol. 2016 Apr 12;2:9 - PubMed
- Int J Obes (Lond). 2010 Aug;34(8):1255-64 - PubMed
- J Diabetes Res. 2013;2013:429154 - PubMed
- J Clin Endocrinol Metab. 2003 Apr;88(4):1637-45 - PubMed
- Diabetes Metab Res Rev. 2014 Feb;30(2):96-102 - PubMed
- Asian Pac J Trop Biomed. 2012 Sep;2(9):691-5 - PubMed
- Ann Intern Med. 2016 Sep 6;165(5):305-15 - PubMed
- Expert Rev Gastroenterol Hepatol. 2014 May;8(4):343-9 - PubMed
- JAMA. 2008 Apr 2;299(13):1561-73 - PubMed
- J Biol Chem. 2006 Mar 31;281(13):8748-55 - PubMed
- Arterioscler Thromb. 1991 Jul-Aug;11(4):1068-76 - PubMed
- Diab Vasc Dis Res. 2012 Jan;9(1):52-8 - PubMed
- Diabet Med. 2005 Aug;22(8):980-5 - PubMed
- Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):182-8 - PubMed
- Hepatology. 2004 Jan;39(1):188-96 - PubMed
- Curr Pharm Des. 2013;19(29):5177-92 - PubMed
- Am J Physiol Endocrinol Metab. 2003 Jun;284(6):E1125-30 - PubMed
- Nutrients. 2013 May 10;5(5):1544-60 - PubMed
- Br J Pharmacol. 2010 Dec;161(8):1708-21 - PubMed
- J Clin Invest. 2001 Oct;108(8):1167-74 - PubMed
- Endocrinology. 2010 Jan;151(1):85-95 - PubMed
- Endocrinol Metab Clin North Am. 2014 Mar;43(1):75-102 - PubMed
- Ther Adv Endocrinol Metab. 2015 Apr;6(2):56-60 - PubMed
- Biofactors. 2004;20(1):37-47 - PubMed
- Metabolism. 2006 Aug;55(8):996-1001 - PubMed
- N Engl J Med. 1995 Aug 31;333(9):541-9 - PubMed
- Pak J Pharm Sci. 2010 Jul;23(3):305-12 - PubMed
- Arterioscler Thromb Vasc Biol. 2003 Dec;23(12):2203-8 - PubMed
- Lipids Health Dis. 2015 Dec 03;14:158 - PubMed
- J Clin Invest. 2006 Jul;116(7):1813-22 - PubMed
- N Engl J Med. 1999 Jan 14;340(2):115-26 - PubMed
- Sci Rep. 2016 Sep 16;6:33386 - PubMed
- Biomed Rep. 2013 Jan;1(1):57-64 - PubMed
- Vasc Health Risk Manag. 2007;3(6):967-73 - PubMed
- Clin Biochem Rev. 2005 May;26(2):19-39 - PubMed
- N Engl J Med. 1995 Aug 31;333(9):550-4 - PubMed
- J Res Med Sci. 2014 Jul;19(7):658-64 - PubMed
- Hypertens Res. 2007 Jan;30(1):23-30 - PubMed
- J Clin Invest. 1999 Feb;103(3):365-72 - PubMed
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