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Cardiac insulin signaling

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https://www.readbyqxmd.com/read/28821796/cathepsin-k-knockout-protects-against-cardiac-dysfunction-in-diabetic-mice
#1
Rui Guo, Yinan Hua, Olivia Rogers, Travis E Brown, Jun Ren, Sreejayan Nair
Diabetes is a major risk factor for cardiovascular disease and the lysosomal cysteine protease cathepsin K plays a critical role in cardiac pathophysiology. To expand upon our previous findings, we tested the hypothesis that, knockout of cathepsin K protects against diabetes-associated cardiac anomalies. Wild-type and cathepsin K knockout mice were rendered diabetic by streptozotocin (STZ) injections. Body weight, organ mass, fasting blood glucose, energy expenditure, cardiac geometry and function, cardiac histomorphology, glutathione levels and protein levels of cathepsin K and those associated with Ca(2+) handling, calcineurin/NFAT signaling, insulin signaling, cardiac apoptosis and fibrosis were determined...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28781146/the-impact-of-foxo-1-to-cardiac-pathology-in-diabetes-mellitus-and-diabetes-related-metabolic-abnormalities
#2
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Diabetic heart pathology has a serious social impact due to high prevalence worldwide and significant mortality/invalidation of diabetic patients suffered from cardiomyopathy. The pathogenesis of diabetic and diabetes-related cardiomyopathy is associated with progressive loss and impairment of cardiac function due to adverse effects of metabolic, prooxidant, proinflammatory, and pro-apoptotic stress factors. In the adult heart, the transcriptional factor forkhead box-1 (FOXO-1) is involved in maintaining cardiomyocytes in the homeostatic state and induction of their adaptation to metabolic and pro-oxidant stress stimuli...
August 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28743802/enhancing-natriuretic-peptide-signaling-in-adipose-tissue-but-not-in-muscle-protects-against-diet-induced-obesity-and-insulin-resistance
#3
Wei Wu, Fubiao Shi, Dianxin Liu, Ryan P Ceddia, Robert Gaffin, Wan Wei, Huafeng Fang, E Douglas Lewandowski, Sheila Collins
In addition to controlling blood pressure, cardiac natriuretic peptides (NPs) can stimulate lipolysis in adipocytes and promote the "browning" of white adipose tissue. NPs may also increase the oxidative capacity of skeletal muscle. To unravel the contribution of NP-stimulated metabolism in adipose tissue compared to that in muscle in vivo, we generated mice with tissue-specific deletion of the NP clearance receptor, NPRC, in adipose tissue (Nprc(AKO) ) or in skeletal muscle (Nprc(MKO) ). We showed that, similar to Nprc null mice, Nprc(AKO) mice, but not Nprc(MKO) mice, were resistant to obesity induced by a high-fat diet...
July 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28739173/lipid-droplet-proteins-and-metabolic-diseases
#4
REVIEW
Shimeng Xu, Xuelin Zhang, Pingsheng Liu
Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which are composed of a neutral lipid core bounded by a protein decorated phospholipid monolayer. Although lipid storage is their most obvious function, LDs are far from inert as they participate in maintaining lipid homeostasis through lipid synthesis, metabolism, and transportation. Furthermore, they are involved in cell signaling and other molecular events closely associated with human disease such as dyslipidemia, obesity, lipodystrophy, diabetes, fatty liver, atherosclerosis, and others...
July 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28736261/genetic-disruption-of-the-cardiomyocyte-circadian-clock-differentially-influences-insulin-mediated-processes-in-the-heart
#5
Graham R McGinnis, Yawen Tang, Rachel A Brewer, Manoja K Brahma, Haley L Stanley, Gobinath Shanmugam, Namakkal Soorappan Rajasekaran, Glenn C Rowe, Stuart J Frank, Adam R Wende, E Dale Abel, Heinrich Taegtmeyer, Silvio Litovsky, Victor Darley-Usmar, Jianhua Zhang, John C Chatham, Martin E Young
Cardiovascular physiology exhibits time-of-day-dependent oscillations, which are mediated by both extrinsic (e.g., environment/behavior) and intrinsic (e.g., circadian clock) factors. Disruption of circadian rhythms negatively affects multiple cardiometabolic parameters. Recent studies suggest that the cardiomyocyte circadian clock directly modulates responsiveness of the heart to metabolic stimuli (e.g., fatty acids) and stresses (e.g., ischemia/reperfusion). The aim of this study was to determine whether genetic disruption of the cardiomyocyte circadian clock impacts insulin-regulated pathways in the heart...
July 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28735097/protecting-the-heart-through-mk2-modulation-toward-a-role-in-diabetic-cardiomyopathy-and-lipid-metabolism
#6
REVIEW
Matthieu Ruiz, Lise Coderre, Bruce Gordon Allen, Christine Des Rosiers
Various signaling pathways have been identified in the heart as important players during development, physiological adaptation or pathological processes. This includes the MAPK families, particularly p38MAPK, which is involved in several key cellular processes, including differentiation, proliferation, apoptosis, inflammation, metabolism and survival. Disrupted p38MAPK signaling has been associated with several diseases, including cardiovascular diseases (CVD) as well as diabetes and its related complications...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28714796/effect-of-bariatric-surgery-on-heart-failure
#7
Marcela Rodriguez Flores, Carlos Aguilar Salinas, Marie-Eve Piché, Audrey Auclair, Paul Poirier
Obesity increases the risk of heart failure (HF), which continues to be a significant proportion of all cardiovascular diseases and affects increasingly younger populations. The cross-talk between adipose and the heart involves insulin resistance, adipokine signaling and inflammation, with the capacity of adipose tissue to mediate hemodynamic signals, promoting progressive cardiomyopathy. Areas covered: From a therapeutic perspective, there is not yet a single obesity-related pathway that when addressed, can ameliorate cardiomyopathy in obese patients and this is a matter of ongoing research...
August 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28698617/loss-of-md1-exacerbates-pressure-overload-induced-left-ventricular-structural-and-electrical-remodelling
#8
Jianye Peng, Yu Liu, Xiaoju Xiong, Congxin Huang, Yang Mei, Zhiqiang Wang, Yanhong Tang, Jing Ye, Bin Kong, Wanli Liu, Teng Wang, He Huang
Myeloid differentiation protein 1 (MD1) has been implicated in numerous pathophysiological processes, including immune regulation, obesity, insulin resistance, and inflammation. However, the role of MD1 in cardiac remodelling remains incompletely understood. We used MD1-knockout (KO) mice and their wild-type littermates to determine the functional significance of MD1 in the regulation of aortic banding (AB)-induced left ventricular (LV) structural and electrical remodelling and its underlying mechanisms. After 4 weeks of AB, MD1-KO hearts showed substantial aggravation of LV hypertrophy, fibrosis, LV dilation and dysfunction, and electrical remodelling, which resulted in overt heart failure and increased electrophysiological instability...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28680407/cardiac-ion-channel-regulation-in-obesity-and-the-metabolic-syndrome-relevance-to-long-qt-syndrome-and-atrial-fibrillation
#9
REVIEW
Ademuyiwa S Aromolaran, Mohamed Boutjdir
Obesity and its associated metabolic dysregulation leading to metabolic syndrome is an epidemic that poses a significant public health problem. More than one-third of the world population is overweight or obese leading to enhanced risk of cardiovascular disease (CVD) incidence and mortality. Obesity predisposes to atrial fibrillation, ventricular, and supraventricular arrhythmias; conditions that are underlain by dysfunction in electrical activity of the heart. To date, current therapeutic options for cardiomyopathy of obesity are limited, suggesting that there is considerable room for development of therapeutic interventions with novel mechanisms of action that will help normalize rhythm in obese patients...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28677741/mulberry-granules-protect-against-diabetic-cardiomyopathy-through-the-ampk-nrf2-pathway
#10
Yang Liu, Yan-Bo Zhao, Si-Wang Wang, Yu Zhou, Zhi-Shu Tang, Feng Li
Mulberry granules (MLD) is a traditional Chinese medicine prescription that has been used in the treatment of diabetes for many years. Recently, we found that MLD protected the heart from diabetes-associated cardiomyopathy when it was used to treat diabetes. However, the beneficial effects and possible mechanism remain unknown. To elucidate these effects, an experimental myocardial ischemia/reperfusion (MI/R) injury model in diabetes rats was used in this study. Male C57BL/6 mice were injected with streptozotocin to induce diabetes...
July 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28676923/biochemical-and-pharmacological-role-of-a1-adenosine-receptors-and-their-modulation-as-novel-therapeutic-strategy
#11
Katia Varani, Fabrizio Vincenzi, Stefania Merighi, Stefania Gessi, Pier Andrea Borea
Adenosine, the purine nucleoside, mediates its effects through activation of four G-protein coupled adenosine receptors (ARs) named as A1, A2A, A2B and A3. In particular, A1ARs are distributed through the body, primarily inhibitory in the regulation of adenylyl cyclase activity and able to reduce the cyclic AMP levels. Considerable advances have been made in the pharmacological and molecular characterization of A1ARs, which had been proposed as targets for the discovery and drug design of antagonists, agonists and allosteric enhancers...
July 5, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28676430/insulin-regulates-titin-pre-mrna-splicing-through-the-pi3k-akt-mtor-kinase-axis-in-a-rbm20-dependent-manner
#12
Chaoqun Zhu, Zhiyong Yin, Bihua Tan, Wei Guo
Titin, a giant sarcomeric protein, is largely responsible for the diastolic properties of the heart. It has two major isoforms, N2B and N2BA due to pre-mRNA splicing regulated mainly by a splicing factor RNA binding motif 20 (RBM20). Mis-splicing of titin pre-mRNA in response to external stimuli may lead to altered ratio of N2B to N2BA, and thus, impaired cardiac contractile function. However, little is known about titin alternative splicing in response to external stimuli. Here, we reported the detailed mechanisms of titin alternative splicing in response to insulin...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28659817/cobalt-chloride-upregulates-impaired-hif-1%C3%AE-expression-to-restore-sevoflurane-post-conditioning-dependent-myocardial-protection-in-diabetic-rats
#13
Jianjiang Wu, Long Yang, Peng Xie, Jin Yu, Tian Yu, Haiying Wang, Yiliyaer Maimaitili, Jiang Wang, Haiping Ma, Yining Yang, Hong Zheng
Previous studies from our group have demonstrated that sevoflurane post-conditioning (SPC) protects against myocardial ischemia reperfusion injury via elevating the intranuclear expression of hypoxia inducible factor-1 alpha (HIF-1α). However, diabetic SPC is associated with decreased myocardial protection and disruption of the HIF-1 signaling pathway. Previous studies have demonstrated that cobalt chloride (CoCl2) can upregulate HIF-1α expression under diabetic conditions, but whether myocardial protection by SPC can be restored afterward remains unclear...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28643218/empagliflozin-improves-left-ventricular-diastolic-dysfunction-in-a-genetic-model-of-type-2-diabetes
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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