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Sitagliptin and cardiomyocytes

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https://www.readbyqxmd.com/read/29325553/sitagliptin-improved-glucose-assimilation-in-detriment-of-fatty-acid-utilization-in-experimental-type-ii-diabetes-role-of-glp-1-isoforms-in-glut4-receptor-trafficking
#1
E Ramírez, B Picatoste, A González-Bris, M Oteo, F Cruz, A Caro-Vadillo, J Egido, J Tuñón, M A Morcillo, Ó Lorenzo
BACKGROUND: The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. METHODS: Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18 F]-2-fluoro-2-deoxy-D-glucose (18 FDG)...
January 11, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27284355/sitagliptin-attenuates-in%C3%AF-ammatory-responses-in-lipopolysaccharide-stimulated-cardiomyocytes-via-nuclear-factor-%C3%AE%C2%BAb-pathway-inhibition
#2
Chien-Hung Lin, Chung-Ching Lin
Glucagon-like peptide-1 (GLP-1) and GLP-1 receptors (GLP-1Rs) are responsible for glucose homeostasis, and have been shown to reduce inflammation in preclinical studies. The aim of the present study was to determine whether sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), as a GLP-1 receptor agonist, exerts an anti-inflammatory effect on cardiomyoblasts during lipopolysaccharide (LPS) stimulation. Exposure to LPS increased the expression levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL)-6 and IL-1β in H9c2 cells, and also resulted in elevations in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression and nuclear factor-κB (NF-κB) nuclear translocation...
June 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/25837922/sitagliptin-alleviated-myocardial-remodeling-of-the-left-ventricle-and-improved-cardiac-diastolic-dysfunction-in-diabetic-rats
#3
Yu-Sheng Liu, Zhi-Wei Huang, Lin Wang, Xin-Xin Liu, Yong-Mei Wang, Yun Zhang, Mei Zhang
OBJECTIVE: Sitagliptin, a dipeptidyl peptidase IV (DPP-Ⅳ) inhibitor, has a biological role in improving the serum levels of glucagon-like peptide 1 (GLP-1). Hence, we sought to determine the effect of sitagliptin on myocardial inflammation, collagen metabolism, lipid content and myocardial apoptosis in diabetic rats. MATERIALS AND METHODS: The type 2 diabetic rat model was induced by low-dose streptozotocin and a high-fat diet. Characteristics of diabetic rats were evaluated by electrocardiography, echocardiography and blood analysis...
March 2015: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/25341892/left-ventricular-diastolic-dysfunction-and-myocardial-stiffness-in-diabetic-mice-is-attenuated-by-inhibition-of-dipeptidyl-peptidase-4
#4
Nazha Hamdani, Anne-Sophie Hervent, Leni Vandekerckhove, Veerle Matheeussen, Marc Demolder, Lesley Baerts, Ingrid De Meester, Wolfgang A Linke, Walter J Paulus, Gilles W De Keulenaer
AIMS: Obesity and Type 2 diabetes mellitus (DM) induce left ventricular (LV) diastolic dysfunction, which contributes to an increasing prevalence of heart failure with a preserved LV ejection fraction. We investigated the effects of sitagliptin (SITA), an inhibitor of dipeptidylpeptidase-4 (DPP-4) and anti-diabetic drug, on LV structure and function of obese mice with Type 2 DM. METHODS AND RESULTS: Obese Type 2 diabetic mice (Lepr(db/db), BKS.Cg-Dock7(m)+/+ Lepr(db)/J), displaying increased cardiomyocyte and LV stiffness at the age of 16 weeks, were treated with SITA (300 mg/kg/day) or vehicle for 8 weeks...
December 1, 2014: Cardiovascular Research
https://www.readbyqxmd.com/read/24302978/sitagliptin-reduces-cardiac-apoptosis-hypertrophy-and-fibrosis-primarily-by-insulin-dependent-mechanisms-in-experimental-type-ii-diabetes-potential-roles-of-glp-1-isoforms
#5
Belén Picatoste, Elisa Ramírez, Alicia Caro-Vadillo, Cristian Iborra, Sara Ares-Carrasco, Jesús Egido, José Tuñón, Oscar Lorenzo
BACKGROUND: Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart. METHODS: Goto-Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies...
2013: PloS One
https://www.readbyqxmd.com/read/24041927/protective-effects-of-sitagliptin-on-myocardial-injury-and-cardiac-function-in-an-ischemia-reperfusion-rat-model
#6
Guanglei Chang, Peng Zhang, Lin Ye, Kai Lu, Ying Wang, Qin Duan, Aihua Zheng, Shu Qin, Dongying Zhang
The purpose of this study is to investigate the effects and the underlying mechanisms of sitagliptin pretreatment on myocardial injury and cardiac function in myocardial ischemia/reperfusion (I/R) rat model. The rat model of myocardial I/R was constructed by coronary occlusion. Rats were pretreated with sitagliptin (300 mg/kg/day) for 2 weeks, and then subjected to 30 min ischemia and 2h reperfusion. The release of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB), cardiac function and cardiomyocyte apoptosis were evaluated...
October 15, 2013: European Journal of Pharmacology
https://www.readbyqxmd.com/read/24012160/the-dipeptidyl-peptidase-4-inhibitor-sitagliptin-modulates-calcium-dysregulation-inflammation-and-ppars-in-hypertensive-cardiomyocytes
#7
T-I Lee, Y-H Kao, Y-C Chen, J-H Huang, M-I Hsu, Y-J Chen
BACKGROUND: Hypertension induces cardiac dysfunction, calcium (Ca(2+)) dysregulation, and arrhythmogenesis. Dipeptidyl peptidase (DPP)-4 inhibitors, an antidiabetic agent with anti-inflammation and anti-hypertension potential, may regulate peroxisome proliferator-activated receptors (PPARs)-α, -γ, and -δ and Ca(2+) homeostasis. OBJECTIVE: The purpose of this study was to investigate whether DPP-4 inhibitor, sitagliptin, can modulate PPARs and Ca(2+) handling proteins in hypertensive hearts...
October 15, 2013: International Journal of Cardiology
https://www.readbyqxmd.com/read/23894014/circulating-dipeptidyl-peptidase-iv-activity-correlates-with-cardiac-dysfunction-in-human-and-experimental-heart-failure
#8
Leonardo dos Santos, Thiago A Salles, Daniel F Arruda-Junior, Luciene C G Campos, Alexandre C Pereira, Ana Luiza T Barreto, Ednei L Antonio, Alfredo J Mansur, Paulo J F Tucci, José E Krieger, Adriana C C Girardi
BACKGROUND: The present study addresses the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction is also investigated. METHODS AND RESULTS: Measurements of DPPIV activity in blood samples obtained from 190 patients with HF and 42 controls demonstrated that patients with HF exhibited an increase of ≈130% in circulating DPPIV activity compared with healthy subjects...
September 1, 2013: Circulation. Heart Failure
https://www.readbyqxmd.com/read/23051671/dipeptidyl-peptidase-iv-inhibition-upregulates-glut4-translocation-and-expression-in-heart-and-skeletal-muscle-of-spontaneously-hypertensive-rats
#9
Gisele Giannocco, Kelen C Oliveira, Renato O Crajoinas, Gabriela Venturini, Thiago A Salles, Miriam H Fonseca-Alaniz, Rui M B Maciel, Adriana C C Girardi
The purpose of the current study was to test the hypothesis that the dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin, which exerts anti-hyperglycemic and anti-hypertensive effects, upregulates GLUT4 translocation, protein levels, and/or mRNA expression in heart and skeletal muscle of spontaneously hypertensive rats (SHRs). Ten days of treatment with sitagliptin (40 mg/kg twice daily) decreased plasma DPPIV activity in both young (Y, 5-week-old) and adult (A, 20-week-old) SHRs to similar extents (~85%)...
January 5, 2013: European Journal of Pharmacology
https://www.readbyqxmd.com/read/21871459/effects-of-dpp-4-inhibition-on-cardiac-metabolism-and-function-in-mice
#10
M Lenski, A Kazakov, N Marx, M Böhm, U Laufs
Type 2 diabetes is associated with an increased risk of cardiac complications. Inhibitors of dipeptidylpeptidase 4 (DPP-4) are novel drugs for the treatment of patients with type 2 diabetes. The effect of DPP-4 inhibitors on myocardial metabolism has not been studied in detail. In wild-type C57Bl6-mice, 3weeks of treatment with sitagliptin had no effect on body weight and glucose tolerance nor on phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoAcarboxylase (ACC), phosphofructokinase-2 (PFK2) or tuberin-2 (TSC2) in the left ventricular myocardium...
December 2011: Journal of Molecular and Cellular Cardiology
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