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Cardiac insulin signaling

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https://www.readbyqxmd.com/read/29898838/randomized-placebo-controlled-trial-evaluating-the-safety-and-efficacy-of-single-low-dose-intracoronary-insulin-like-growth-factor-following-percutaneous-coronary-intervention-in-acute-myocardial-infarction-resus-ami
#1
Noel M Caplice, Mary C DeVoe, Janet Choi, Darren Dahly, Theodore Murphy, Ernest Spitzer, Robert Van Geuns, Michael M Maher, David Tuite, David M Kerins, Mohammed T Ali, Imtiaz Kalyar, Eoin F Fahy, Wisam Khider, Peter Kelly, Peter P Kearney, Ronan J Curtin, Conor O'Shea, Carl J Vaughan, Joseph A Eustace, Eugene P McFadden
BACKGROUND: Residual and significant postinfarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models, low-dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodeling effects. We studied the safety and efficacy of immediate post-PCI low-dose intracoronary IGF1 infusion in STEMI patients...
June 2018: American Heart Journal
https://www.readbyqxmd.com/read/29887522/relaxin-family-member-insulin-like-peptide-6-ameliorates-cardiac-fibrosis-and-prevents-cardiac-remodeling-in-murine-heart-failure-models
#2
Sonomi Maruyama, Chia-Ling Wu, Sumiko Yoshida, Dongying Zhang, Pei-Hsuan Li, Fangzhou Wu, Jennifer Parker Duffen, Rouan Yao, Blake Jardin, Ibrahim M Adham, Ronald Law, Joel Berger, Richard Di Marchi, Kenneth Walsh
BACKGROUND: The insulin/insulin-like growth factor/relaxin family represents a group of structurally related but functionally diverse proteins. The family member relaxin-2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of insulin-like peptide 6 (INSL6), another member of this protein family, in murine heart failure models using genetic loss-of-function and protein delivery methods. METHODS AND RESULTS: Insl6-deficient and wild-type (C57BL/6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively, for 2 weeks...
June 10, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29882416/role-of-insulin-like-growth-factor-1-receptor-signaling-in-stem-cell-stemness-and-therapeutic-efficacy
#3
Chiao-Fang Teng, Long-Bin Jeng, Woei-Cherng Shyu
Evidence has emerged that stem cells represent a promising therapeutic tool for tissue engineering and regenerative medicine. Thus, identifying functional markers for selecting stem cells capable of superior self-renewal and pluripotency (or multipotency) and maintaining stem cell identity under appropriate culture conditions are critical for guiding the use of stem cells toward clinical applications. Many investigations have implicated the insulin-like growth factor 1 receptor (IGF1R) signaling in maintenance of stem cell characteristics and enhancement of stem cell therapy efficacy...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29850600/calcium-signaling-in-the-ventricular-myocardium-of-the-goto-kakizaki-type-2-diabetic-rat
#4
REVIEW
L Al Kury, M Smail, M A Qureshi, V Sydorenko, A Shmygol, M Oz, J Singh, F C Howarth
The association between diabetes mellitus (DM) and high mortality linked to cardiovascular disease (CVD) is a major concern worldwide. Clinical and preclinical studies have demonstrated a variety of diastolic and systolic dysfunctions in patients with type 2 diabetes mellitus (T2DM) with the severity of abnormalities depending on the patients' age and duration of diabetes. The cellular basis of hemodynamic dysfunction in a type 2 diabetic heart is still not well understood. The aim of this review is to evaluate our current understanding of contractile dysfunction and disturbances of Ca2+ transport in the Goto-Kakizaki (GK) diabetic rat heart...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29773993/diabetic-cardiomyopathy-impact-of-biological-sex-on-disease-development-and-molecular-signatures
#5
REVIEW
Ryan Toedebusch, Anthony Belenchia, Lakshmi Pulakat
Diabetic cardiomyopathy refers to a unique set of heart-specific pathological variables induced by hyperglycemia and insulin resistance. Given that cardiovascular disease (CVD) is the leading cause of death in the world, and type 2 diabetes incidence continues to rise, understanding the complex interplay between these two morbidities and developing novel therapeutic strategies is vital. Two hallmark characteristics specific to diabetic cardiomyopathy are diastolic dysfunction and cardiac structural mal-adaptations, arising from cardiac cellular responses to the complex toxicity induced by hyperglycemia with or without hyperinsulinemia...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29760016/diabetes-induced-cardiomyocyte-passive-stiffening-is-caused-by-impaired-insulin-dependent-titin-modification-and-can-be-modulated-by-neuregulin-1
#6
Anna-Eliane Hopf, Christian Andresen, Sebastian Kötter, Malgorzata Isic, Kamila Ulrich, Senem Sahin, Sabine Bongardt, Wilhelm Roell, Felicitas Drove, Nina Scheerer, Leni Vandekerckhove, Gilles W De Keulenaer, Nazha Hamdani, Wolfgang A Linke, Martina Krüger
<u>Rationale:</u> Increased titin-dependent cardiomyocyte tension is a hallmark of heart failure with preserved ejection fraction (HFpEF) associated with type-2 diabetes mellitus (T2DM). However, the insulin-related signaling pathways that modify titin-based cardiomyocyte tension, thereby contributing to modulation of diastolic function, are largely unknown. <u>Objective:</u> We aimed to determine how impaired insulin signaling affects titin expression and phosphorylation and thus increases passive cardiomyocyte tension, and whether metformin or neuregulin-1 can correct disturbed titin modifications and increased titin-based stiffness...
May 14, 2018: Circulation Research
https://www.readbyqxmd.com/read/29752038/transient-postnatal-over-nutrition-induces-long-term-alterations-in-cardiac-nlrp3-inflammasome-pathway
#7
B Siddeek, N Li, C Mauduit, H Chehade, E Rigal, J-F Tolsa, J-B Armengaud, C Yzydorczyk, M Benahmed, C Vergely, U Simeoni
BACKGROUND AND AIMS: The prevalence of obesity is increasing worldwide at an alarming rate. Altered early nutrition, in particular postnatal overfeeding (PNOF), is a risk factor for impaired cardiac function in adulthood. In the understanding of the initiation or progression of heart diseases, NLRP3 inflammasome and non-coding RNAs have been proposed as key players. In this context, the aim of this study was to decipher the role of NLRP3 inflammasome and its post transcriptional control by micro-RNAs in the regulation of cardiac metabolic function induced by PNOF in mice...
April 14, 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29731023/heart-failure-with-preserved-ejection-fraction-in-diabetes-mechanisms-and-management
#8
REVIEW
Patrick Meagher, Mohamed Adam, Robert Civitarese, Antoinette Bugyei-Twum, Kim A Connelly
Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as "diabetic cardiomyopathy." Furthermore, heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition...
May 2018: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29720537/isosteviol-ameliorates-diabetic-cardiomyopathy-in-rats-by-inhibiting-erk-and-nf%C3%AE%C2%BAb-signaling-pathways
#9
Shenggao Tang, Xiaoyu Liu, Ji-Ming Ye, Tingting Hu, Yingying Yang, Ting Han, Wen Tan
Diabetes induced injury of myocardium, defined as diabetic cardiomyopathy (DCM), accounts for significant mortality and morbidity in diabetic population. Alleviation of DCM by a potent drug remains considerable interests in experimental and clinical researches because hypoglycemic drugs cannot effectively control this condition. Here we explored the beneficial effects of isosteviol sodium (STVNa) on type 1 diabetes induced DCM and the potential mechanisms involved. Male Wistar rats were induced to diabetes by injection of streptozotocin (STZ)...
May 2, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29719446/ursolic-acid-in-health-and-disease
#10
REVIEW
Dae Yun Seo, Sung Ryul Lee, Jun-Won Heo, Mi-Hyun No, Byoung Doo Rhee, Kyung Soo Ko, Hyo-Bum Kwak, Jin Han
Ursolic acid (UA) is a natural triterpene compound found in various fruits and vegetables. There is a growing interest in UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects. It exerts these effects in various tissues and organs: by suppressing nuclear factor-kappa B signaling in cancer cells, improving insulin signaling in adipose tissues, reducing the expression of markers of cardiac damage in the heart, decreasing inflammation and increasing the level of anti-oxidants in the brain, reducing apoptotic signaling and the level of oxidants in the liver, and reducing atrophy and increasing the expression levels of adenosine monophosphate-activated protein kinase and irisin in skeletal muscles...
May 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29709706/argirein-alleviates-vascular-endothelial-insulin-resistance-through-suppressing-the-activation-of-nox4-dependent-o-2-production-in-diabetic-rats
#11
Qing Li, Jie Su, Shi-Jie Jin, Wei Wei, Xiao-Dong Cong, Xiao-Xue Li, Ming Xu
BACKGROUND: Insulin resistance in endothelial cells contributes to the development of cardiovascular disease in type 2 diabetes mellitus (T2DM). Therefore, there are great potential clinical implications in developing pharmacological interventions targeting endothelial insulin resistance. Our previous studies indicated that argirein which was developed by combining rhein with L-arginine by a hydrogen bond, could substantially relieved stress related exacerbation of cardiac failure and alleviated cardiac dysfunction in T2DM, which was associated with suppressing NADPH oxidase activity...
April 27, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29707604/cyp-450-epoxygenase-derived-epoxyeicosatrienoic-acid-contribute-to-reversal-of-heart-failure-in-obesity-induced-diabetic-cardiomyopathy-via-pgc-1-%C3%AE-activation
#12
S P Singh, J A McClung, L Bellner, J Cao, M Waldman, J Schragenheim, M Arad, E Hochhauser, J R Falck, J A Weingarten, S J Peterson, N G Abraham
We have previously shown that an Epoxyeicosatrienoic Acid (EET) -agonist has pleiotropic effects and reverses cardiomyopathy by decreasing inflammatory molecules and increasing antioxidant signaling. We hypothesized that administration of an EET agonist would increase Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), which controls mitochondrial function and induction of HO-1 and negatively regulates the expression of the proinflammatory adipokines CCN3/NOV in cardiac and pericardial tissues...
2018: Cardiovascular Pharmacology: Open Access
https://www.readbyqxmd.com/read/29590321/polymorphisms-within-ryr3-gene-are-associated-with-risk-and-age-at-onset-of-hypertension-diabetes-and-alzheimer-s-disease
#13
Shaoqing Gong, Brenda Bin Su, Hugo Tovar, ChunXiang Mao, Valeria Gonzalez, Ying Liu, Yongke Lu, Ke-Sheng Wang, Chun Xu
Background: Hypertension affects 33% of Americans while type 2 diabetes and Alzheimer's disease (AD) affect 10% of Americans, respectively. Ryanodine receptor 3 gene (RYR3) codes for the ryanodine receptor which functions to release stored endoplasmic reticulum calcium ions (Ca2+ ) to increase intracellular Ca2+ concentration. Increasing studies demonstrate that altered levels of intracellular Ca2+ affects cardiac contraction, insulin secretion and neurodegeneration. In this study, we investigated associations of the RYR3 genetic variants with hypertension, AD, and diabetes...
March 26, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29581288/small-proline-rich-protein-2b-drives-stress-dependent-p53-degradation-and-fibroblast-proliferation-in-heart-failure
#14
Ryan M Burke, Janet K Lighthouse, Pearl Quijada, Ronald A Dirkx, Alexander Rosenberg, Christine S Moravec, Jeffrey D Alexis, Eric M Small
Heart disease is associated with the accumulation of resident cardiac fibroblasts (CFs) that secrete extracellular matrix (ECM), leading to the development of pathological fibrosis and heart failure. However, the mechanisms underlying resident CF proliferation remain poorly defined. Here, we report that small proline-rich protein 2b ( Sprr2b ) is among the most up-regulated genes in CFs during heart disease. We demonstrate that SPRR2B is a regulatory subunit of the USP7/MDM2-containing ubiquitination complex...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29577579/hepatic-and-cardiac-beneficial-effects-of-a-long-acting-fc-apelin-fusion-protein-in-diet-induced-obese-mice
#15
Weimin Wang, Dongming Zhang, Rongze Yang, Wei Xia, Kun Qian, Zhengrong Shi, Robert Brown, Huifen Zhou, Yue Xi, Lin Shi, Ling Chen, Feng Xu, Xiaojian Sun, Dalong Zhu, Da-Wei Gong
BACKGROUND: Apelin is a peptide ligand of the G-protein-coupled receptor APJ and exhibits anti-diabetes and anti-heart failure activities. However, short serum half-life of the apelin peptide limits its potential clinical applications. This study aimed to develop a long-acting apelin analog. METHODS: To extend apelin's in vivo half-life, we made a recombinant protein by fusing the IgG Fc fragment to apelin-13 (Fc-apelin-13), conducted pharmacokinetics studies in mice, and determined in vitro biological activities in suppressing cyclic adenosine monophosphate and activating extracellular signal-regulated kinase signalling by reporter assays...
March 25, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29566382/testosterone-deprivation-aggravates-left-ventricular-dysfunction-in-male-obese-insulin-resistant-rats-via-impairing-cardiac-mitochondrial-function-and-dynamics-proteins
#16
Nattayaporn Apaiajai, Titikorn Chunchai, Thidarat Jaiwongkam, Sasiwan Kerdphoo, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: We have previously reported that testosterone deprivation at a very young age accelerated, but did not aggravate, left-ventricular (LV) dysfunction in obese insulin-resistant rats. However, the effects of testosterone deprivation during adulthood on LV function in obese insulin-resistant rats remains unclear. We hypothesized that testosterone deprivation aggravates LV dysfunction and cardiac autonomic imbalance via the impairment of cardiac mitochondrial function and dynamics proteins, a reduction in insulin receptor function, and an increase in apoptosis in obese insulin-resistant rats...
March 22, 2018: Gerontology
https://www.readbyqxmd.com/read/29542814/effects-of-ramelteon-on-cardiac-injury-and-adipose-tissue-pathology-in-rats-with-metabolic-syndrome
#17
Ayako Uchinaka, Yuri Kawashima, Yuki Sano, Shogo Ito, Yusuke Sano, Kai Nagasawa, Natsumi Matsuura, Mamoru Yoneda, Yuichiro Yamada, Toyoaki Murohara, Kohzo Nagata
Melatonin regulates circadian rhythms but also has antioxidative and anti-inflammatory effects that ameliorate metabolic disorders. We investigated the effects of the selective melatonin agonist ramelteon on cardiac and adipose tissue pathology in the DahlS.Z-Leprfa /Leprfa (DS/obese) rat, a model of metabolic syndrome (MetS). Rats were treated with a low (0.3 mg/kg per day) or high (8 mg/kg per day) dose of ramelteon from 9 to 13 weeks of age. Ramelteon treatment at either dose attenuated body weight gain, left ventricular fibrosis, and diastolic dysfunction, as well as cardiac oxidative stress and inflammation, without affecting hypertension or insulin resistance...
March 15, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29484207/cardiac-development-and-transcription-factors-insulin-signalling-insulin-resistance-and-intrauterine-nutritional-programming-of-cardiovascular-disease
#18
REVIEW
Annelene Govindsamy, Strinivasen Naidoo, Marlon E Cerf
Programming with an insult or stimulus during critical developmental life stages shapes metabolic disease through divergent mechanisms. Cardiovascular disease increasingly contributes to global morbidity and mortality, and the heart as an insulin-sensitive organ may become insulin resistant, which manifests as micro- and/or macrovascular complications due to diabetic complications. Cardiogenesis is a sequential process during which the heart develops into a mature organ and is regulated by several cardiac-specific transcription factors...
2018: Journal of Nutrition and Metabolism
https://www.readbyqxmd.com/read/29467020/insulin-like-growth-factor-1-mediated-regulation-of-mir-193a-expression-promotes-the-migration-and-proliferation-of-c-kit-positive-mouse-cardiac-stem-cells
#19
Yuning Sun, Rongfeng Xu, Jia Huang, Yuyu Yao, Xiaodong Pan, Zhongpu Chen, Genshan Ma
BACKGROUND: C-kit-positive cardiac stem cells (CSCs) have been shown to be a promising candidate treatment for myocardial infarction and heart failure. Insulin-like growth factor (IGF)-1 is an anabolic growth hormone that regulates cellular proliferation, differentiation, senescence, and death in various tissues. Although IGF-1 promotes the migration and proliferation of c-kit-positive mouse CSCs, the underlying mechanism remains unclear. METHODS: Cells were isolated from adult mouse hearts, and c-kit-positive CSCs were separated using magnetic beads...
February 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29449364/diabetic-cardiomyopathy-an-update-of-mechanisms-contributing-to-this-clinical-entity
#20
REVIEW
Guanghong Jia, Michael A Hill, James R Sowers
Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy...
February 16, 2018: Circulation Research
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