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Metformin and cardioprotection

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https://www.readbyqxmd.com/read/29165830/possible-protective-mechanisms-exerted-by-metformin-or-metformin-and-vitamin-e-in-isoproterenol-induced-cardiac-injury
#1
Nawal M Al-Rasheed, Nouf M Al-Rasheed, Danah A Al-Rabeeah, Heba S Al-Barrak, Salma A Al-Salman, Shahd A Ibrahim, Sulafa A Al-Hassab, Maha A Al-Amin, Iman H Hasan, Hanaa N Al-Ajmi, Tahani K Al-Shammari
Several studies have reported that metformin is cardioprotective for diabetic and non-diabetic ischemic hearts through mechanisms that cannot be entirely attributed to its anti-hyperglycemic effect. This study was designed to investigate the cardioprotective effects of metformin with and without vitamin E after induction myocardial infarction (MI) in rats, using isoproterenol. Administration of metformin or vitamin E significantly reduced the cardiac mass index (P<0.01), ameliorated the changes to cardiac biomarkers, and attenuated oxidative stress levels compared to the isoproterenol group...
November 22, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29139080/a-review-of-insulin-resistance-in-type-1-diabetes-is-there-a-place-for-adjunctive-metformin
#2
REVIEW
Gagan Priya, Sanjay Kalra
There is a rising trend of overweight and obesity among individuals with type 1 diabetes. This is often associated with insulin resistance, increased insulin dose requirements and poor glycemic control. Insulin resistance is also seen during puberty and is strongly related to increased risk of cardiovascular disease. The role of metformin as an adjunct to ongoing intensive insulin therapy in type 1 diabetics has been evaluated in several randomized trials, including the recently concluded T1D Exchange Network trial in adolescents and the REMOVAL trial in adults...
November 14, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29137475/metformin-attenuates-myocardium-dicarbonyl-stress-induced-by-chronic-hypertriglyceridemia
#3
H Malinska, V Škop, J Trnovska, I Markova, P Svoboda, L Kazdova, M Haluzik
Reactive dicarbonyls stimulate production of advanced glycation endproducts, increase oxidative stress and inflammation and contribute to the development of vascular complications. We measured concentrations of dicarbonyls - methylglyoxal (MG), glyoxal (GL) and 3-deoxyglucosone (3-DG) - in the heart and kidney of a model of metabolic syndrome - hereditary hypertriglyceridemic rats (HHTg) and explored its modulation by metformin. Adult HHTg rats were fed a standard diet with or without metformin (300 mg/kg b...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/28947430/sirt2-acts-as-a-cardioprotective-deacetylase-in-pathological-cardiac-hypertrophy
#4
Xiaoqiang Tang, Xiao-Feng Chen, Nan-Yu Wang, Xiao-Man Wang, Shu-Ting Liang, Wei Zheng, Yun-Biao Lu, Xiang Zhao, De-Long Hao, Zhu-Qin Zhang, Ming-Hui Zou, De-Pei Liu, Hou-Zao Chen
BACKGROUND: Pathological cardiac hypertrophy induced by stresses such as aging and neurohumoral activation is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)-induced pathological cardiac hypertrophy. METHODS: Male C57BL/6J wild-type and Sirt2 knockout mice were subjected to the investigation of aging-related cardiac hypertrophy...
November 21, 2017: Circulation
https://www.readbyqxmd.com/read/28870455/pharmacological-evaluation-of-metformin-and-n-benzylbiguanide-a-novel-analogue-of-metformin-on-the-vasopressor-responses-to-adrenergic-system-stimulation-in-pithed-rats-with-fructose-induced-insulin-resistance
#5
Erika J Gutiérrez-Lara, Gabriel Navarrete-Vázquez, Araceli Sánchez-López, David Centurión
Metformin has been associated with cardioprotection, vasorelaxation and normalization of endothelial function during type 2 Diabetes Mellitus. However, few studies have analysed its effects on vascular adrenergic system. Our study has evaluated the vasopressor responses induced by sympathetic stimulation or by i.v. bolus injections of the agonists noradrenaline (α1/2), methoxamine (α1) and UK 14,304 (α2) in rats with fructose-induced insulin resistance chronically pretreated with either metformin or EGL-6M (N-benzylbiguanide), a novel analogue of metformin...
November 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28819951/metformin-a-new-old-drug
#6
Marta Patrycja Wróbel, Bogdan Marek, Dariusz Kajdaniuk, Dominika Rokicka, Aleksandra Szymborska-Kajanek, Krzysztof Strojek
For many years metformin has been the gold standard in the treatment of type 2 diabetes. According to recommendations of the most important diabetes associations, this is the first-choice drug for use as monotherapy in patients with newly diagnosed type 2 diabetes. Metformin is also recommended in combined treatment when monotherapy is no longer effective. It is then combined with a sulfony-lurea, an incretin, flozin, or insulin, irrespective of the number of insulin injections per day. Besides its properties used in the treatment of diabetes, metformin has been treated for some time as a drug of a so-called pleiotropic activity, as each year brings new reports about its favourable effect in different conditions...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28770321/metformin-clinical-use-in-type-2-diabetes
#7
REVIEW
Elizabeth Sanchez-Rangel, Silvio E Inzucchi
Metformin is one of the most popular oral glucose-lowering medications, widely considered to be the optimal initial therapy for patients with type 2 diabetes mellitus. Interestingly, there still remains controversy regarding the drug's precise mechanism of action, which is thought to involve a reduction in hepatic glucose production. It is now recommended as first-line treatment in various guidelines, including that of the EASD and ADA. Its favoured status lies in its efficacy, low cost, weight neutrality and good safety profile...
September 2017: Diabetologia
https://www.readbyqxmd.com/read/28755285/two-year-follow-up-of-4%C3%A2-months-metformin-treatment-vs-placebo-in-st-elevation-myocardial-infarction-data-from-the-gips-iii-rct
#8
Minke H T Hartman, Jake K B Prins, Remco A J Schurer, Erik Lipsic, Chris P H Lexis, Anouk N A van der Horst-Schrivers, Dirk J van Veldhuisen, Iwan C C van der Horst, Pim van der Harst
OBJECTIVES: Preclinical and clinical studies suggested cardioprotective effects of metformin treatment. In the GIPS-III trial, 4 months of metformin treatment did not improve left ventricular ejection fraction in patients presenting with ST-elevation myocardial infarction (STEMI). Here, we report the 2-year follow-up results. METHODS: Between January 2011 and May 2013, 379 STEMI patients without diabetes undergoing primary percutaneous coronary intervention were randomized to a 4-month treatment with metformin (500 mg twice daily) (N = 191) or placebo (N = 188) in the University Medical Center Groningen...
July 28, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28643448/postconditioning-with-metformin-attenuates-apoptotic-events-in-cardiomyoblasts-associated-with-ischemic-reperfusion-injury
#9
Rajesh Ramachandran, Mini Saraswathi
AIM: Ischemic postconditioning is considered as a potent method to combat ischemic reperfusion injury than preconditioning and rapid initiation of reperfusion with potent antioxidant compounds can be one of the most effective treatments to reduce the infarct size and behavioral deficits as a result of ischemic insult. The present study aims to determine the postconditioning effects of metformin in experimental ischemia. METHODS: H9C2 cells were subjected to experimental ischemia and reperfused with metformin...
June 23, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28579457/metformin-ameliorates-gender-and-age-dependent-hemodynamic-instability-and-myocardial-injury-in-murine-hemorrhagic-shock
#10
Dzmitry Matsiukevich, Giovanna Piraino, Patrick Lahni, Paul W Hake, Vivian Wolfe, Michael O'Connor, Jeanne James, Basilia Zingarelli
Severity of multiple organ failure is significantly impacted by age and gender in patients with hemorrhagic shock. However, the molecular mechanisms underlying the enhanced organ injury are not fully understood. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of metabolic responses during stress. We investigated whether hemorrhage-induced myocardial injury is age and gender dependent and whether treatment with metformin, an AMPK activator, affords cardioprotective effects. C57/BL6 young (3-5months) and mature (9-12months) male and female mice were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with blood and Lactated Ringer's solution...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28499942/metformin-ameliorates-hypoxia-reoxygenation-induced-cardiomyocyte-apoptosis-based-on-the-sirt3-signaling-pathway
#11
Yanyan Du, Jingjing Zhang, Fang Fang, Xiqing Wei, Hongsheng Zhang, Hongyong Tan, Jinguo Zhang
Myocardial hypoxia/reoxygenation (H/R) injury is one of the main causes of death and disability worldwide. However, a limited number of therapies are available to minimize the detrimental effects of this injury. Recently, researchers have demonstrated that metformin exerts direct cardioprotective effects against H/R. The aim of this study was to investigate the underlying mechanisms of how metformin affects myocardial hypoxia/reoxygenation (H/R) injury. In our study, the activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the levels of malondialdehyde (MDA) were measured...
August 30, 2017: Gene
https://www.readbyqxmd.com/read/28410530/metformin-attenuated-endotoxin-induced-acute-myocarditis-via-activating-ampk
#12
Gang Liu, Kejia Wu, Li Zhang, Jie Dai, Wei Huang, Ling Lin, Pu Ge, Fuling Luo, Han Lei
Metformin is a widely used anti-diabetic drug and increasing evidence suggests that metformin have profound cardioprotective effects under both diabetic and non-diabetic situations. The protective benefits of metformin have been proved in diabetic patients with cardiovascular complications and in experimental animals with myocardial infarction and cardiac hypertrophy. In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in endotoxin-challenged mice...
April 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28332871/sodium-glucose-cotransporter-2-and-dipeptidyl-peptidase-4-inhibition-promise-of-a-dynamic-duo
#13
REVIEW
Ildiko Lingvay
OBJECTIVE: This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM). METHODS: We conducted a nonsystematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States. RESULTS: SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiologic abnormalities present in T2DM without overlapping toxicities...
July 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28298952/insights-for-oxidative-stress-and-mtor-signaling-in-myocardial-ischemia-reperfusion-injury-under-diabetes
#14
REVIEW
Dajun Zhao, Jian Yang, Lifang Yang
Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27788262/resveratrol-reverses-functional-chagas-heart-disease-in-mice
#15
Glaucia Vilar-Pereira, Vitor C Carneiro, Hilton Mata-Santos, Amanda R R Vicentino, Isalira P Ramos, Naira L L Giarola, Daniel F Feijó, José R Meyer-Fernandes, Heitor A Paula-Neto, Emiliano Medei, Marcelo T Bozza, Joseli Lannes-Vieira, Claudia N Paiva
Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27687032/impact-of-bromocriptine-qr-therapy-on-cardiovascular-outcomes-in-type-2-diabetes-mellitus-subjects-on-metformin
#16
RANDOMIZED CONTROLLED TRIAL
Bindu Chamarthi, Michael Ezrokhi, Dean Rutty, Anthony H Cincotta
OBJECTIVES: Type 2 diabetes mellitus (T2DM) is associated with a substantially increased risk of cardiovascular disease (CVD). Bromocriptine-QR (B-QR), a quick release sympatholytic dopamine D2 receptor agonist, is a FDA-approved therapy for T2DM which may provide CVD risk reduction. Metformin is considered to be an agent with a potential cardioprotective benefit. This large placebo controlled clinical study assessed the impact of B-QR addition to existing metformin therapy on CVD outcomes in T2DM subjects...
November 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27669556/metformin-synergizes-with-conventional-and-adjuvant-analgesic-drugs-to-reduce-inflammatory-hyperalgesia-in-rats
#17
Uroš B Pecikoza, Maja A Tomić, Ana M Micov, Radica M Stepanović-Petrović
BACKGROUND: Metformin is a widely used and safe antidiabetic drug that has recently been shown to possess analgesic properties in models of inflammatory pain. Because various arthritic inflammatory disorders are highly prevalent in diabetic patients, we aimed to examine the type of interaction between metformin and several conventional and adjuvant analgesic drugs (ibuprofen, aspirin, tramadol, and pregabalin) in a rat model of somatic inflammatory hyperalgesia. METHODS: Inflammation of the rat hind paw was induced by an intraplantar injection of carrageenan (0...
April 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27621180/metformin-protects-against-infection-induced-myocardial-dysfunction
#18
Theodora Tzanavari, Aimilia Varela, Stamatis Theocharis, Elpinickie Ninou, Alkistis Kapelouzou, Dennis V Cokkinos, Maria I Kontaridis, Katia P Karalis
BACKGROUND AND PURPOSE: Metformin administration is associated with myocardial protection during ischemia and/or reperfusion, possibly via inhibition of inflammatory responses in the heart. Exposure to pathogens, in addition to the activation of the immune system and the associated metabolic dysfunction, often results in compromised myocardial function. We examined whether metformin administration could maintain the normal myocardial function in experimental moderate Gram negative infection, induced by lipopolysaccharide (LPS) administration...
October 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27561827/metformin-improves-circulating-endothelial-cells-and-endothelial-progenitor-cells-in-type-1-diabetes-merit-study
#19
MULTICENTER STUDY
Fahad W Ahmed, Rachel Rider, Michael Glanville, Kilimangalam Narayanan, Salman Razvi, Jolanta U Weaver
BACKGROUND: Type 1 diabetes is associated with increased cardiovascular disease (CVD). Decreased endothelial progenitor cells (EPCs) number plays a pivotal role in reduced endothelial repair and development of CVD. We aimed to determine if cardioprotective effect of metformin is mediated by increasing circulating endothelial progenitor cells (cEPCs), pro-angiogenic cells (PACs) and decreasing circulating endothelial cells (cECs) count whilst maintaining unchanged glycemic control. METHODS: This study was an open label and parallel standard treatment study...
August 26, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27465053/phosphodiesterase-type-5-inhibitor-use-in-type-2-diabetes-is-associated-with-a-reduction-in-all-cause-mortality
#20
Simon G Anderson, David C Hutchings, Mark Woodward, Kazem Rahimi, Martin K Rutter, Mike Kirby, Geoff Hackett, Andrew W Trafford, Adrian H Heald
OBJECTIVE: Experimental evidence has shown potential cardioprotective actions of phosphodiesterase type-5 inhibitors (PDE5is). We investigated whether PDE5i use in patients with type 2 diabetes, with high-attendant cardiovascular risk, was associated with altered mortality in a retrospective cohort study. RESEARCH DESIGN AND METHODS: Between January 2007 and May 2015, 5956 men aged 40-89 years diagnosed with type 2 diabetes before 2007 were identified from anonymised electronic health records of 42 general practices in Cheshire, UK, and were followed for 7...
November 1, 2016: Heart: Official Journal of the British Cardiac Society
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