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Cardiac insulin signaling

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https://www.readbyqxmd.com/read/28643218/empagliflozin-improves-left-ventricular-diastolic-dysfunction-in-a-genetic-model-of-type-2-diabetes
#1
Nadjib Hammoudi, Dongtak Jeong, Rajvir Singh, Ahmed Farhat, Michel Komajda, Eric Mayoux, Roger Hajjar, Djamel Lebeche
PURPOSE: Cardiovascular (CV) diseases in type 2 diabetes (T2DM) represent an enormous burden with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as a new antidiabetic class that improves glucose control, as well as body weight and blood pressure with no increased risk of hypoglycemia. The first CV outcome study terminated with empagliflozin, a specific SGLT2 inhibitor, has shown a reduction in CV mortality and in heart failure hospitalization, suggesting a beneficial impact on cardiac function which remains to be demonstrated...
June 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28618996/the-influence-of-obese-insulin-resistance-on-the-outcome-of-the-ischemia-reperfusion-insult-to-the-heart
#2
Krekwit Shinlapawittayatorn, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: Obese insulin-resistance is one of the most important risk factor for cardiovascular diseases including ischemic heart disease (IHD). Growing evidences suggest that the susceptibility to myocardial ischemia-reperfusion (I/R) injury is increased in an obese insulin-resistance condition. Based on the currently available evidence from human and animal studies, this review mainly focuses on the influence of obese insulin-resistance on the outcome of the I/R insult to the heart...
June 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28601616/fructose-rich-diet-and-insulin-action-in-female-rat-heart-estradiol-friend-or-foe
#3
REVIEW
Maja Bundalo, Snjezana Romic, Snezana Tepavcevic, Mojca Stojiljkovic, Aleksandra Stankovic, Maja Zivkovic, Goran Koricanac
Increased intake of fructose in humans and laboratory animals is demonstrated to be a risk factor for development of metabolic disorders (insulin resistance, metabolic syndrome, type 2 diabetes) and cardiovascular diseases. On the other hand, estradiol is emphasized as a cardioprotective agent. The main goal of this review is to summarize recent findings on damaging cardiac effects of fructose-rich diet in females, mostly experimental animals, and to evaluate protective capacity of estradiol. Published results of our and other research groups indicate mostly detrimental effects of fructose-rich diet on cardiac insulin signaling molecules, glucose and fatty acid metabolism, nitric oxide production and ion transport, as well as renin-angiotensin system and inflammation...
June 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28593918/beyond-obesity-thermogenic-adipocytes-and-cardiometabolic-health
#4
Peter Aldiss, Neele Dellschaft, Harold Sacks, Helen Budge, Michael E Symonds
The global prevalence of obesity and related cardiometabolic disease continues to increase through the 21st century. Whilst multi-factorial, obesity is ultimately caused by chronic caloric excess. However, despite numerous interventions focussing on reducing caloric intake these either fail or only elicit short-term changes in body mass. There is now a focus on increasing energy expenditure instead which has stemmed from the recent 're-discovery' of cold-activated brown adipose tissue (BAT) in adult humans and inducible 'beige' adipocytes...
May 26, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28576832/eet-intervention-on-wnt1-nov-and-ho-1-signaling-prevents-obesity-induced-cardiomyopathy-in-obese-mice
#5
Jian Cao, Shailendra P Singh, John McClung, Gregory Joseph, Luca Vanella, Ignazio Barbagallo, Houli Jiang, John R Falck, Michael Arad, Joseph I Shapiro, Nader G Abraham
We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on vascular function, in addition to its anti-apoptotic action, it increases insulin sensitivity and inhibits inflammation. To uncover the signaling mechanisms by which EET reduces cardiomyopathy, we hypothesized that EET infusion might ameliorate obesity-induced cardiomyopathy by improving HO-1, Wnt1, thermogenic gene levels and mitochondrial integrity in cardiac tissues and improved pericardial fat phenotype. EET reduced levels of fasting blood glucose, and pro-inflammatory adipokines including NOV signaling while increasing echocardiographic fractional shortening and O2 consumption...
June 2, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28573188/a-hyper-crosslinked-carbohydrate-polymer-scaffold-facilitates-lineage-commitment-and-maintains-a-reserve-pool-of-proliferating-cardiovascular-progenitors
#6
Jonathan M Baio, Ryan C Walden, Tania I Fuentes, Charles C Lee, Nahidh W Hasaniya, Leonard L Bailey, Mary K Kearns-Jonker
BACKGROUND: Cardiovascular progenitor cells (CPCs) have been cultured on various scaffolds to resolve the challenge of cell retention after transplantation and to improve functional outcome after cell-based cardiac therapy. Previous studies have reported successful culture of fully differentiated cardiomyocytes on scaffolds of various types, and ongoing efforts are focused on optimizing the mix of cardiomyocytes and endothelial cells as well as on the identification of a source of progenitors capable of reversing cardiovascular damage...
May 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28560388/inhibition-of-igf-1-receptor-kinase-blocks-the-differentiation-into-cardiomyocyte-like-cells-of-bmscs-induced-by-igf-1
#7
Haibin Gong, Xiuli Wang, Lei Wang, Ying Liu, Jie Wang, Qian Lv, Hui Pang, Qinglin Zhang, Zhenquan Wang
Bone marrow mesenchymal stem cells (BMSCs) have the potential to transdifferentiate into cardiomyocyte‑like cells (CLCs) if an appropriate cardiac environment is provided. Insulin‑like growth factor‑1 (IGF‑1) plays an important role in the cell migration, survival and differentiation of BMSCs. However, the effect of IGF‑1 on the cellular differentiation remains unclear. In the present study, BMSCs were isolated from rat femurs and tibias and the cells were purified at passage 6 (P6). IGF‑1 and IGF‑1 receptor (IGF‑1R) kinase inhibitor I‑OMe AG538 were added to detect if IGF‑1 could induce BMSCs to transdifferentiate into CLCs and if I‑OMe AG538 could inhibit IGF‑1‑mediated receptor activation and downstream signaling...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28549591/single-allele-lmbrd1-knockout-results-in-cardiac-hypertrophy
#8
Linda Tzu-Ling Tseng, Chieh-Liang Lin, Kuei-Hsiang Pan, Kai-Yuan Tzen, Ming-Jai Su, Chia-Ti Tsai, Yi-Han Li, Pai-Chi Li, Fu-Tien Chiang, Shin C Chang, Ming-Fu Chang
BACKGROUND/PURPOSE: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear. METHODS: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system...
May 23, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28546469/green-tea-egcg-enhances-cardiac-function-restoration-through-expression-of-survival-signaling-in-dm-rats-with-autologous-adipose-tissue-derived-stem-cell
#9
Tung-Sheng Chen, Show-Yih Liou, Chia-Hua Kuo, Lung-Fa Pan, Yu-Lan Yeh, Jeffery Liou, V Vijaya Padma, Chun-Hsu Yao, Wei-Wen Kuo, Chih-Yang Huang
The present study tests a hypothesis that cardioprotective effects mediated by autologous adipose-derived stem cells (ADSC) in rats afflicted with insulin-dependent diabetes mellitus (IDDM), may be synergistically enhanced by oral treatment with green tea epigallocatechin gallat (ECCG). Wistar rats were divided into sham, DM, DM+ADSC (autologous transplanted 1x106 cells/rat) and DM+ADSC+E (E, green tea oral administration EGCG). Heart tissues were isolated for all rats and investigations were performed after 2-months treatment...
May 25, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28534118/exercise-induced-circulating-extracellular-vesicles-protect-against-cardiac-ischemia-reperfusion-injury
#10
Yihua Bei, Tianzhao Xu, Dongchao Lv, Pujiao Yu, Jiahong Xu, Lin Che, Avash Das, John Tigges, Vassilios Toxavidis, Ionita Ghiran, Ravi Shah, Yongqin Li, Yuhui Zhang, Saumya Das, Junjie Xiao
Extracellular vesicles (EVs) serve an important function as mediators of intercellular communication. Exercise is protective for the heart, although the signaling mechanisms that mediate this cardioprotection have not been fully elucidated. Here using nano-flow cytometry, we found a rapid increase in plasma EVs in human subjects undergoing exercise stress testing. We subsequently identified that serum EVs were increased by ~1.85-fold in mice after 3-week swimming. Intramyocardial injection of equivalent quantities of EVs from exercised mice and non-exercised controls provided similar protective effects against acute ischemia/reperfusion (I/R) injury in mice...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#11
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28467921/molecular-mechanisms-underlying-cardiac-adaptation-to-exercise
#12
REVIEW
Rick B Vega, John P Konhilas, Daniel P Kelly, Leslie A Leinwand
Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart, and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long-term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension...
May 2, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28449155/mitochondrial-dysfunction-in-diabetic-cardiomyopathy-effect-of-mesenchymal-stem-cell-with-ppar-%C3%AE-agonist-or-exendin-4
#13
Mohamed Abd Elaziz Wassef, Ola M Tork, Laila A Rashed, Walaa Ibrahim, Heba Morsi, Dina Mohamed Mekawy Rabie
Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4...
April 27, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28434143/the-mtor-signaling-pathway-in-myocardial-dysfunction-in-type-2-diabetes-mellitus
#14
REVIEW
Tomohiro Suhara, Yuichi Baba, Briana K Shimada, Jason K Higa, Takashi Matsui
PURPOSE OF REVIEW: T2DM (type 2 diabetes mellitus) is a risk factor for heart failure. The mTOR (mechanistic target of rapamycin) is a key mediator of the insulin signaling pathway. We will discuss the role of mTOR in myocardial dysfunction in T2DM. RECENT FINDINGS: In T2DM, chronically activated mTOR induces multiple pathological events, including a negative feedback loop that suppresses IRS (insulin receptor substrate)-1. While short-term treatment with rapamycin, an mTOR inhibitor, is a promising strategy for cardiac diseases such as acute myocardial infarction and cardiac hypertrophy in T2DM, there are many concerns about chronic usage of rapamycin...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28432201/mg53-biological-function-and-potential-as-a-therapeutic-target
#15
Yan Zhang, Hong-Kun Wu, Fengxiang Lv, Rui-Ping Xiao
MG53 (also known as TRIM72) is a cardiac and skeletal muscle-specific TRIM-family protein that exhibits multiple biological functions. First, MG53 participates in plasma membrane repair of the heart, skeletal muscle and other tissues. Second, MG53 is essentially involved in the cardioprotection of cardiac ischemic, pre-conditioning and post-conditioning, by activating the PI3K-Akt-GSK3β and ERK1/2 survival signaling pathways. Moreover, systemic delivery of recombinant MG53 protein ameliorates the impact of a range of injury insults on heart, skeletal muscle, lung, kidney, skin and brain...
April 21, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28420091/dietary-sugars-and-endogenous-formation-of-advanced-glycation-endproducts-emerging-mechanisms-of-disease
#16
REVIEW
Manuela Aragno, Raffaella Mastrocola
The rapid increase in metabolic diseases, which occurred in the last three decades in both industrialized and developing countries, has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as a consequence of a high dietary sugar intake. Animal models of high sugar consumption, in particular fructose, have reported AGE accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations...
April 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28412087/pregestational-type-2-diabetes-mellitus-induces-cardiac%C3%A2-hypertrophy-in-the-murine-embryo-through-cardiac%C3%A2-remodeling-and-fibrosis
#17
Xue Lin, Penghua Yang, E Albert Reece, Peixin Yang
BACKGROUND: Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus. Experimental evidence has implied that pregnant women with type 2 diabetes mellitus and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study revealed that maternal type 2 diabetes mellitus induces structural heart defects in their offspring. OBJECTIVE: This study aims to determine whether maternal type 2 diabetes mellitus induces embryonic heart hypertrophy in a murine model of diabetic embryopathy...
April 13, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28404627/multiphasic-regulation-of-systemic-and-peripheral-organ-metabolic-responses-to-cardiac-hypertrophy
#18
Chong Wee Liew, Shanshan Xu, Xuerong Wang, Maximilian McCann, Hyerim Whang Kong, Andrew C Carley, Jingbo Pang, Giamila Fantuzzi, J Michael O'Donnell, E Douglas Lewandowski
BACKGROUND: Reduced fat oxidation in hypertrophied hearts coincides with a shift of carnitine palmitoyl transferase I from muscle to increased liver isoforms. Acutely increased carnitine palmitoyl transferase I in normal rodent hearts has been shown to recapitulate the reduced fat oxidation and elevated atrial natriuretic peptide message of cardiac hypertrophy. METHODS AND RESULTS: Because of the potential for reduced fat oxidation to affect cardiac atrial natriuretic peptide, and thus, induce adipose lipolysis, we studied peripheral and systemic metabolism in male C57BL/6 mice model of transverse aortic constriction in which left ventricular hypertrophy occurred by 2 weeks without functional decline until 16 weeks (ejection fraction, -45...
April 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28396530/downregulation-of-plzf-gene-ameliorates-metabolic-and-cardiac-traits-in-the-spontaneously-hypertensive-rat
#19
František Liška, Vladimír Landa, Václav Zídek, Petr Mlejnek, Jan Šilhavý, Miroslava Šimáková, Hynek Strnad, Jaroslava Trnovská, Vojtěch Škop, Ludmila Kazdová, Colby G Starker, Daniel F Voytas, Zsuzsanna Izsvák, Massimiliano Mancini, Ondřej Šeda, Vladimír Křen, Michal Pravenec
The spontaneously hypertensive rat (SHR), one of the most widely used model of essential hypertension, is predisposed to left ventricular hypertrophy, myocardial fibrosis, and metabolic disturbances. Recently, quantitative trait loci influencing blood pressure, left ventricular mass, and heart interstitial fibrosis were genetically isolated within a minimal congenic subline that contains only 7 genes, including mutant Plzf (promyelocytic leukemia zinc finger) candidate gene. To identify Plzf as a quantitative trait gene, we targeted Plzf in the SHR using the transcription activator-like effector nuclease technique and obtained SHR line harboring targeted Plzf gene with a premature stop codon...
June 2017: Hypertension
https://www.readbyqxmd.com/read/28395010/inflammation-and-metabolic-cardiomyopathy
#20
Kazuhiko Nishida, Kinya Otsu
Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signalling pathways are directly triggered by nutrients. The pro-inflammatory mediators in adipocytes and macrophages infiltrating adipose tissue promote both local and systemic pro-inflammatory status...
March 15, 2017: Cardiovascular Research
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