Cardioprotective Effects of Metformin and Vildagliptin in Adult Rats with Insulin Resistance Induced by a High-Fat Diet

Endocrinology - Tập 153 Số 8 - Trang 3878-3885 - 2012
Nattayaporn Apaijai1, Hiranya Pintana1, Siriporn C. Chattipakorn1,2,3, Nipon Chattipakorn4,1
1Cardiac Electrophysiology Research and Training Center (N.A., H.P., S.C.C., N.C.), Chiang Mai, 50200, Thailand
2Faculty of Medicine
3Faculty of Medicine; Faculty of Dentistry (S.C.C.), Chiang Mai, 50200, Thailand
4Biomedical Engineering Center (N.C.), Chiang Mai University, Chiang Mai, 50200, Thailand

Tóm tắt

Insulin resistance has been shown to be associated with cardiac sympathovagal imbalance, myocardial dysfunction, and cardiac mitochondrial dysfunction. Whereas metformin is a widely used antidiabetic drug to improve insulin resistance, vildagliptin is a novel oral antidiabetic drug in a group of dipeptidyl peptidase-4 inhibitors in which its cardiac effect is unclear. This study aimed to determine the cardiovascular effects of metformin and vildagliptin in rats with insulin resistance induced by high-fat diet. Male Wistar rats were fed with either a normal diet or high-fat diet (n =24 each) for 12 wk. Rats in each group were divided into three subgroups to receive the vehicle, metformin (30 mg/kg, twice daily), or vildagliptin (3 mg/kg, once daily) for another 21 d. Heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined and compared among these treatment groups. Rats exposed to a high-fat diet developed increased body weight, visceral fat, plasma insulin, cholesterol, oxidative stress, depressed HRV, and cardiac mitochondrial dysfunction. Metformin and vildagliptin did not alter body weight and plasma glucose levels but decreased the plasma insulin, total cholesterol, and oxidative stress levels. Although both metformin and vildagliptin attenuated the depressed HRV, cardiac dysfunction, and cardiac mitochondrial dysfunction, vildagliptin was more effective in this prevention. Furthermore, only vildagliptin prevented cardiac mitochondrial membrane depolarization caused by consumption of a high-fat diet. We concluded that vildagliptin is more effective in preventing cardiac sympathovagal imbalance and cardiac dysfunction, as well as cardiac mitochondrial dysfunction, than metformin in rats with insulin resistance induced by high-fat diet.

Từ khóa


Tài liệu tham khảo

Costa, 2011, High fat diet induces central obesity, insulin resistance and microvascular dysfunction in hamsters., Microvasc Res, 82, 416, 10.1016/j.mvr.2011.08.007

Pipatpiboon, 2012, PPARγ agonist improves neuronal insulin receptor function in hippocampus and brain mitochondria function in rats with insulin resistance induced by long term high-fat diets., Endocrinology, 153, 329, 10.1210/en.2011-1502

Pratchayasakul, 2011, Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone., Life Sci, 88, 619, 10.1016/j.lfs.2011.02.003

Ouwens, 2007, Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification., Diabetologia, 50, 1938, 10.1007/s00125-007-0735-8

Raher, 2008, A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload., Am J Physiol Heart Circ Physiol, 295, H2495, 10.1152/ajpheart.00139.2008

Pongchaidecha, 2009, Effects of curcuminoid supplement on cardiac autonomic status in high-fat-induced obese rats., Nutrition, 25, 870, 10.1016/j.nut.2009.02.001

Eurich, 2007, Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review., BMJ, 335, 497, 10.1136/bmj.39314.620174.80

Palee, 2011, PPARγ activator, rosiglitazone: is it beneficial or harmful to the cardiovascular system?, World J Cardiol, 3, 144, 10.4330/wjc.v3.i5.144

Khurana, 2010, Metformin: safety in cardiac patients., Postgrad Med J, 86, 371, 10.1136/hrt.2009.173773

Wang, 2011, Metformin improves cardiac function in rats via activation of AMP-activated protein kinase., Clin Exp Pharmacol Physiol, 38, 94, 10.1111/j.1440-1681.2010.05470.x

Verma, 1994, Metformin improves cardiac function in isolated streptozotocin-diabetic rat hearts., Am J Physiol, 266, H714

Gundewar, 2009, Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure., Circ Res, 104, 403, 10.1161/CIRCRESAHA.108.190918

Zander, 2002, Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study., Lancet, 359, 824, 10.1016/S0140-6736(02)07952-7

Chinda, 2012, Cardioprotective effects of incretin during ischaemia-reperfusion, Diab Vasc Dis Res, 10.1177/1479164112440816

Ito, 2011, The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin improves glycemic control in type 2 diabetic patients undergoing hemodialysis., Endocr J, 58, 979, 10.1507/endocrj.EJ11-0025

Yin, 2011, Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure., Cardiovasc Diabetol, 10, 85, 10.1186/1475-2840-10-85

Dirkx, 2011, High fat diet induced diabetic cardiomyopathy., Prostaglandins Leukot Essent Fatty Acids, 85, 219, 10.1016/j.plefa.2011.04.018

Jin, 2009, Reduced antidiabetic effect of metformin and down-regulation of hepatic Oct1 in rats with ethynylestradiol-induced cholestasis., Pharm Res, 26, 549, 10.1007/s11095-008-9770-5

Burkey, 2005, Acute and chronic effects of the incretin enhancer vildagliptin in insulin-resistant rats., J Pharmacol Exp Ther, 315, 688, 10.1124/jpet.105.087064

Ming, 2011, Absence of meal-induced insulin sensitization (AMIS) in aging rats is associated with cardiac dysfunction that is protected by antioxidants., J Appl Physiol, 111, 704, 10.1152/japplphysiol.00057.2011

Thephinlap, 2011, Reversal of cardiac iron loading and dysfunction in thalassemic mice by curcuminoids., Med Chem, 7, 62, 10.2174/157340611794072724

Mateos, 2005, Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress. Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits., J Chromatogr B Analyt Technol Biomed Life Sci, 827, 76, 10.1016/j.jchromb.2005.06.035

Incharoen, 2007, Heart rate variability in β-thalassemic mice., Int J Cardiol, 121, 203, 10.1016/j.ijcard.2006.08.076

Kumfu, 2012, T-type calcium channel blockade improves survival and cardiovascular function in thalassemic mice., Eur J Haematol, 88, 535, 10.1111/j.1600-0609.2012.01779.x

Ohuchi, 2000, Heart rate recovery after exercise and cardiac autonomic nervous activity in children., Pediatr Res, 47, 329, 10.1203/00006450-200003000-00008

Thummasorn, 2011, Granulocyte-colony stimulating factor attenuates mitochondrial dysfunction induced by oxidative stress in cardiac mitochondria., Mitochondrion, 11, 457, 10.1016/j.mito.2011.01.008

Eriksson, 2007, Short-term effects of metformin in type 2 diabetes., Diabetes Obes Metab, 9, 330, 10.1111/j.1463-1326.2006.00611.x

Cai, 2011, The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials, J Clin Pharm Ther

Dorella, 1996, Improvement of insulin sensitivity by metformin treatment does not lower blood pressure of nonobese insulin-resistant hypertensive patients with normal glucose tolerance., J Clin Endocrinol Metab, 81, 1568

Anurag, 2002, Metformin improves lipid metabolism and attenuates lipid peroxidation in high fructose-fed rats., Diabetes Obes Metab, 4, 36, 10.1046/j.1463-1326.2002.00178.x

Mari, 2005, Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed β-cell function in patients with type 2 diabetes., J Clin Endocrinol Metab, 90, 4888, 10.1210/jc.2004-2460

Ahrén, 2004, Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes., J Clin Endocrinol Metab, 89, 2078, 10.1210/jc.2003-031907

Edgerton, 2009, Inhibition of dipeptidyl peptidase-4 by vildagliptin during glucagon-like peptide 1 infusion increases liver glucose uptake in the conscious dog., Diabetes, 58, 243, 10.2337/db08-0515

Matikainen, 2006, Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes., Diabetologia, 49, 2049, 10.1007/s00125-006-0340-2

Rosenstock, 2007, Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial., Diabetes Care, 30, 217, 10.2337/dc06-1815

Urakawa, 2003, Oxidative stress is associated with adiposity and insulin resistance in men., J Clin Endocrinol Metab, 88, 4673, 10.1210/jc.2003-030202

Chattipakorn, 2007, Heart rate variability in myocardial infarction and heart failure., Int J Cardiol, 120, 289, 10.1016/j.ijcard.2006.11.221

Lombardi, 1987, Heart rate variability as an index of sympathovagal interaction after acute myocardial infarction., Am J Cardiol, 60, 1239, 10.1016/0002-9149(87)90601-1

Van De Borne, 1999, Hyperinsulinemia produces cardiac vagal withdrawal and nonuniform sympathetic activation in normal subjects., Am J Physiol, 276, R178

Manzella, 2004, Blood pressure and cardiac autonomic nervous system in obese type 2 diabetic patients: effect of metformin administration., Am J Hypertens, 17, 223, 10.1016/j.amjhyper.2003.11.006

Hintz, 2003, Insulin resistance induces hyperleptinemia, cardiac contractile dysfunction but not cardiac leptin resistance in ventricular myocytes., Int J Obes Relat Metab Disord, 27, 1196, 10.1038/sj.ijo.0802389

Ouwens, 2005, Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats., Diabetologia, 48, 1229, 10.1007/s00125-005-1755-x

Yin, 2011, Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure., Am J Physiol Heart Circ Physiol, 301, H459, 10.1152/ajpheart.00054.2011

Xie, 2011, Improvement of cardiac functions by chronic metformin treatment is associated with enhanced cardiac autophagy in diabetic OVE26 mice., Diabetes, 60, 1770, 10.2337/db10-0351

Kravchuk, 2011, The effect of metformin on the myocardial tolerance to ischemia-reperfusion injury in the rat model of diabetes mellitus type II., Exp Diabetes Res, 2011, 907496, 10.1155/2011/907496

Kim, 2008, Role of mitochondrial dysfunction in insulin resistance., Circ Res, 102, 401, 10.1161/CIRCRESAHA.107.165472

Palee, 2011, Effect of rosiglitazone on cardiac electrophysiology, infarct size and mitochondrial function in ischaemia and reperfusion of swine and rat heart., Exp Physiol, 96, 778, 10.1113/expphysiol.2011.057885

Chinda, 2012, Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury, Int J Cardiol

Thông tin
Thông tin xuất bản

Endocrinology

Tập 153 Số 8

3878-3885

Thông tin tác giả