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Insulin signaling heart

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https://www.readbyqxmd.com/read/28214558/small-heterodimer-partner-shp-contributes-to-insulin-resistance-in-cardiomyocytes
#1
Ricardo Rodríguez-Calvo, Dipanjan Chanda, Yvonne Oligschlaeger, Marie Miglianico, Will A Coumans, Emma Barroso, Marta Tajes, Joost Jfp Luiken, Jan Fc Glatz, Manuel Vázquez-Carrera, Dietbert Neumann
Small heterodimer partner (SHP) is an atypical nuclear receptor expressed in heart that has been shown to inhibit the hypertrophic response. Here, we assessed the role of SHP in cardiac metabolism and inflammation. Mice fed a high-fat diet (HFD) displayed glucose intolerance accompanied by increased cardiac mRNA levels of Shp. In HL-1 cardiomyocytes, SHP overexpression inhibited both basal and insulin-stimulated glucose uptake and impaired the insulin signalling pathway (evidenced by reduced AKT and AS160 phosphorylation), similar to insulin resistant cells generated by high palmitate/high insulin treatment (HP/HI; 500μM/100nM)...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28209382/err%C3%AE-a-junior-orphan-with-a-senior-role-in-metabolism
#2
REVIEW
Jagannath Misra, Don-Kyu Kim, Hueng-Sik Choi
Estrogen-related receptor (ERR)γ is an orphan nuclear hormone receptor that belongs to the ERR subfamily of transcription factors. No endogenous ligand has been identified to date. ERRγ possesses ligand-independent transcriptional activity that is regulated by co-regulator interactions, and post-translational modifications (PTMs). Recent data from animal models have established ERRγ as a crucial mediator of multiple endocrine and metabolic signals. ERRγ plays important roles in pathological conditions such as insulin resistance, alcoholic liver injury, and cardiac hypertrophy, and controls energy metabolism in the heart, skeletal muscle, and pancreatic β cells...
February 13, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28202772/high-throughput-screening-of-tyrosine-kinase-inhibitor-cardiotoxicity-with-human-induced-pluripotent-stem-cells
#3
Arun Sharma, Paul W Burridge, Wesley L McKeithan, Ricardo Serrano, Praveen Shukla, Nazish Sayed, Jared M Churko, Tomoya Kitani, Haodi Wu, Alexandra Holmström, Elena Matsa, Yuan Zhang, Anusha Kumar, Alice C Fan, Juan C Del Álamo, Sean M Wu, Javid J Moslehi, Mark Mercola, Joseph C Wu
Tyrosine kinase inhibitors (TKIs), despite their efficacy as anticancer therapeutics, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen U.S. Food and Drug Administration-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28192884/myoinositol-ameliorates-high-fat-diet-and-streptozotocin-induced-diabetes-in-rats-through-promoting-insulin-receptor-signaling
#4
Poovathumkal James Antony, Gopalsamy Rajiv Gandhi, Antony Stalin, Kedike Balakrishna, Erenius Toppo, Kuppusamy Sivasankaran, Savarimuthu Ignacimuthu, Naif Abdullah Al-Dhabi
Mimosa pudica Linn. (Mimosaceae) has been traditionally used for the management of type 2 diabetes mellitus (T2DM) in India. The present study evaluates the therapeutic efficacy of myoinositol (25 and 50mg/kg) isolated from M. pudica stem methanol extract in Triton WR-1339 induced hyperlipidemic and high-fat diet (HFD) fed-streptozotocin (STZ)-induced insulin-resistant diabetic rats. Lipid biomarkers, fasting blood glucose (FBG), changes in body weight, food and water intakes, plasma insulin, HOMA-IR, oral glucose tolerance, intraperitoneal insulin tolerance, urea, creatinine, marker enzymes of liver function, β-cell function and the expression levels of insulin receptor-induced signaling molecules were studied...
February 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28183786/extracellular-rnas-are-associated-with-insulin-resistance-and-metabolic-phenotypes
#5
Ravi Shah, Venkatesh Murthy, Michael Pacold, Kirsty Danielson, Kahraman Tanriverdi, Martin G Larson, Kristina Hanspers, Alexander Pico, Eric Mick, Jared Reis, Sarah de Ferranti, Elizaveta Freinkman, Daniel Levy, Udo Hoffmann, Stavroula Osganian, Saumya Das, Jane E Freedman
OBJECTIVE: Insulin resistance (IR) is a hallmark of obesity and metabolic disease. Circulating extracellular RNAs (ex-RNAs), stable RNA molecules in plasma, may play a role in IR, though most studies on ex-RNAs in IR are small. We sought to characterize the relationship between ex-RNAs and metabolic phenotypes in a large community-based human cohort. RESEARCH DESIGN AND METHODS: We measured circulating plasma ex-RNAs in 2,317 participants without diabetes in the Framingham Heart Study (FHS) Offspring Cohort at cycle 8 and defined associations between ex-RNAs and IR (measured by circulating insulin level)...
February 9, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28179397/dipeptidyl-peptidase-4-induces-aortic-valve-calcification-by-inhibiting-insulin-like-growth-factor-1-signaling-in-valvular-interstitial-cells
#6
Bongkun Choi, Sahmin Lee, Sang-Min Kim, Eun-Jin Lee, Sun Ro Lee, Dae-Hee Kim, Jeong Yoon Jang, Sang-Wook Kang, Ki-Up Lee, Eun-Ju Chang, Jae-Kwan Song
Background -Calcification of the aortic valve leads to increased leaflet stiffness, and consequently to the development of calcific aortic valve disease (CAVD); however, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes CAVD progression. Methods -We obtained the aortic valve tissues from humans and murine models (wild type and eNOS(-/-) mice), and cultured the valvular interstitial cells (VICs) and valvular endothelial cells (VECs) from the cusps...
February 8, 2017: Circulation
https://www.readbyqxmd.com/read/28137218/metabolic-and-cardiovascular-actions-of-nesfatin-1-implications-in-health-and-disease
#7
Naresh Ramesh, Kavishankar Gawli, Venkatakiran Pasupulleti, Suraj Unniappan
BACKGROUND: Metabolic homeostasis is achieved by proper functioning of a complex endocrine milieu, comprising of signals arising from the brain and peripheral tissues. Our knowledge of the factors regulating such balance is rapidly evolving, as new signaling molecules are characterized. Of central interest is nesfatin-1, owing to its multifunctional tissue specific actions regulating food intake, body weight, blood glucose and cardiac functions. METHOD: This review discusses the tissue/system wide distribution and actions of nesfatin-1 in regulating metabolic and cardiovascular functions in healthy conditions and diseases...
January 30, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28135006/contribution-of-maladaptive-adipose-tissue-expansion-to-development-of-cardiovascular-disease
#8
Guanghong Jia, Yan Jia, James R Sowers
The overweight and obesity epidemic has led to an increase in the metabolic syndrome and associated cardiovascular disease (CVD). These abnormalities include insulin resistance, type 2 diabetes mellitus, vascular stiffness, hypertension, stroke, and coronary heart disease. Visceral white adipocyte tissue (WAT) expansion and associated fibrosis/stiffness of WAT promote insulin resistance and CVD through increases in proinflammatory adipokines, oxidative stress, activation of renin-angiotensin-aldosterone system, dysregulation of adipocyte apoptosis and autophagy, dysfunctional immune modulation, and adverse changes in the gut microbiome...
December 6, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/28123501/identification-of-the-molecular-mechanisms-underlying-dilated-cardiomyopathy-via-bioinformatic-analysis-of-gene-expression-profiles
#9
Hu Zhang, Zhuo Yu, Jianchao He, Baotong Hua, Guiming Zhang
In the present study, gene expression profiles of patients with dilated cardiomyopathy (DCM) were re-analyzed with bioinformatics tools to investigate the molecular mechanisms underlying DCM. Gene expression dataset GSE3585 was downloaded from Gene Expression Omnibus, which included seven heart biopsy samples obtained from patients with DCM and five healthy controls. Differential analysis was performed using a Limma package in R to screen for differentially expressed genes (DEGs). Functional enrichment analysis was subsequently conducted for DEGs using the Database for Annotation, Visualization and Integration Discovery...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28123046/pde5-inhibitor-tadalafil-and-hydroxychloroquine-co-treatment-provides-synergistic-protection-against-type-2-diabetes-and-myocardial-infarction-in-mice
#10
Rui Wang, Lei Xi, Rakesh C Kukreja
Diabetes is associated with high risk of ischemic heart disease. We previously showed that phosphodiesterase 5 inhibitor - tadalafil (TAD) induces cardioprotection against ischemia/ reperfusion (I/R) injury in diabetic mice. Hydroxychloroquine (HCQ) is a widely used antimalarial and anti-inflammatory drug, which was reported to reduce hyperglycemia in diabetic patients. Therefore we hypothesized that combination of TAD and HCQ may induce synergistic cardioprotection in diabetes. We also investigated the role of insulin-Akt-mTOR signaling, which regulates protein synthesis and cell survival...
January 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28109123/sodium-butyrate-protects-against-high-fat-diet-induced-cardiac-dysfunction-and-metabolic-disorders-in-type-ii-diabetic-mice
#11
Ling Zhang, Jianfeng Du, Naohiro Yano, Hao Wang, Yu Tina Zhao, Dubielecka-Szczerba Patricia, Shougang Zhuang, Eugene Y Chin, Gangjian Qin, Ting C Zhao
Histone deacetylases are recently identified to act as key regulators for cardiac pathophysiology and metabolic disorders. However, the function of histone deacetylase (HDAC) in controlling cardiac performance in type II diabetes and obesity remains unknown. Here we determine whether HDAC inhibition attenuates high fat diet (HFD)-induced cardiac dysfunction and improves metabolic features. Adult mice were fed with either HFD or standard chow food for 24 weeks. Starting at 12 weeks, mice were divided into four groups randomly, in which sodium butyrate (1%), a potent HDAC inhibitor, was provided to chow and HFD-fed mice in drinking water, respectively...
January 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28107204/non-invasive-blood-glucose-detection-system-based-on-conservation-of-energy-method
#12
Yang Zhang, Jian-Ming Zhu, Yong-Bo Liang, Hong-Bo Chen, Shi-Min Yin, Zhen-Cheng Chen
The most common method used for minimizing the occurrence of diabetes complications is frequent glucose testing to adjust the insulin dose. However, using blood glucose (BG) meters presents a risk of infection. It is of great importance to develop non-invasive BG detection techniques. To realize high-accuracy, low-cost and continuous glucose monitoring, we have developed a non-invasive BG detection system using a mixed signal processor 430 (MSP430) microcontroller. This method is based on the combination of the conservation-of-energy method with a sensor integration module, which collects physiological parameters, such as the blood oxygen saturation (SPO2), blood flow velocity and heart rate...
January 20, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28096202/hasf-c3orf58-is-a-novel-ligand-of-the-insulin-like-growth-factor-1-receptor
#13
Akshay Bareja, Conrad Hodgkinson, Alan Payne, Richard Pratt, Victor Dzau
We have recently shown that Hypoxia and Akt induced Stem cell Factor (HASF) protects the heart from ischemia-induced damage and promotes cardiomyocyte proliferation. While we have identified certain signaling pathways responsible for these protective effects, the receptor mediating these effects was unknown. Here, we undertook studies to identify the HASF receptor. A yeast two-hybrid screen identified a partial fragment of Insulin-like Growth Factor 1 Receptor (IGF1R) as a binding partner of HASF. Subsequent co-immunoprecipitation experiments showed that HASF bound to full-length IGF1R...
January 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28057308/drosophila-as-a-model-for-diabetes-and-diseases-of-insulin-resistance
#14
P Graham, L Pick
Despite the importance of insulin signaling pathways in human disease, initial concerns that insect physiology and sugar metabolism differ enough from humans that flies would not model human disease hampered research in this area. However, during the past 10-15 years, evidence has accumulated that flies can indeed model various aspects of diabetes and related human disorders. This cluster of diseases impact insulin and insulin signaling pathways, fields which have been discussed in many excellent review articles in recent years...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28042033/feeding-cycle-dependent-circulating-insulin-fluctuation-is-not-a-dominant-zeitgeber-for-mouse-peripheral-clocks-except-in-the-liver-differences-between-endogenous-and-exogenous-insulin-effects
#15
Katsutaka Oishi, Yuki Yasumoto, Sayaka Higo-Yamamoto, Saori Yamamoto, Naoki Ohkura
The master clock in the suprachiasmatic nucleus synchronizes peripheral clocks via humoral and neural signals in mammals. Insulin is thought to be a critical Zeitgeber (synchronizer) for peripheral clocks because it induces transient clock gene expression in cultured cells. However, the extent to which fluctuations in feeding-dependent endogenous insulin affect the temporal expression of clock genes remains unclear. We therefore investigated the temporal expression profiles of clock genes in the peripheral tissues of mice fed for 8 h during either the daytime (DF) or the nighttime (NF) for one week to determine the involvement of feeding cycle-dependent endogenous insulin rhythms in the circadian regulation of peripheral clocks...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28036029/fenofibrate-therapy-restores-antioxidant-protection-and-improves-myocardial-insulin-resistance-in-a-rat-model-of-metabolic-syndrome-and-myocardial-ischemia-the-role-of-angiotensin-ii
#16
Luz Ibarra-Lara, María Sánchez-Aguilar, Alicia Sánchez-Mendoza, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Elizabeth Carreón-Torres, Eulises Díaz-Díaz, Héctor Vázquez-Meza, Verónica Guarner-Lans, María Esther Rubio-Ruiz
Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia...
December 28, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28029021/bile-acid-nuclear-receptor-farnesoid-x-receptor-therapeutic-target-for-nonalcoholic-fatty-liver-disease
#17
REVIEW
Sun Gi Kim, Byung Kwon Kim, Kyumin Kim, Sungsoon Fang
Nonalcoholic fatty liver disease (NAFLD) is one of the causes of fatty liver, occurring when fat is accumulated in the liver without alcohol consumption. NAFLD is the most common liver disorder in advanced countries. NAFLD is a spectrum of pathology involving hepatic steatosis with/without inflammation and nonalcoholic steatohepatitis with accumulation of hepatocyte damage and hepatic fibrosis. Recent studies have revealed that NAFLD results in the progression of cryptogenic cirrhosis that leads to hepatocarcinoma and cardiovascular diseases such as heart failure...
December 2016: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27989961/role-of-mineralocorticoid-receptor-activation-in-cardiac-diastolic-dysfunction
#18
REVIEW
Guanghong Jia, Yan Jia, James R Sowers
The prevalence of cardiac diastolic dysfunction and heart failure with preserved ejection, a major cause of morbidity and mortality in the western world, is increasing due, in part, to increases in obesity and type 2 diabetes. Characteristics of cardiac diastolic dysfunction include increased myocardial stiffness and impaired left ventricular (LV) relaxation that is characterized by prolonged isovolumic LV relaxation and slow LV filling. Obesity, insulin resistance and type 2 diabetes, especially in females promote activation of mineralocorticoid receptor (MR) signaling with resultant increases in oxidative stress, maladaptive immune responses, inflammation, and impairment of coronary blood flow and cardiac interstitial fibrosis...
October 28, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27983752/high-fat-diet-induces-pka-and-grk-phosphorylation-of-%C3%AE-2-adrenergic-receptor-and-impairs-cardiac-adrenergic-reserve-in-animal-hearts
#19
Qin Fu, Yuting Hu, Qingtong Wang, Yongming Liu, Ning Li, Bing Xu, Sungjin Kim, Nipavan Chiamvimonvat, Yang K Xiang
Patients with diabetes display reduced exercise capability and impaired cardiac contractile reserve to adrenergic stimulation. We have recently uncovered an insulin receptor and adrenergic receptor signal network in the heart. This study aims to understand the impacts of high fat diet (HFD) on the insulin-adrenergic receptor signal network in hearts. Mice with 8 weeks of HFD feeding display diabetes with elevated insulin and glucose levels associated with body weight gain. Mice with HFD feeding have normal cardiac structure and function...
December 16, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27965203/myostatin-propeptide-mutation-of-the-hypermuscular-compact-mice-decreases-the-formation-of-myostatin-and-improves-insulin-sensitivity
#20
Tamas Kocsis, Gyorgy Trencsenyi, Kitti Szabo, Julia Aliz Baan, Geza Muller, Luca Mendler, Ildiko Garai, Hans Reinauer, Ferenc Deak, Laszlo Dux, Aniko Keller-Pinter
The TGF-β family member myostatin (growth/differentiation factor-8, GDF-8) is a negative regulator of skeletal muscle growth. The hypermuscular Compact mice carry the 12-bp Mstn(Cmpt-dl1Abc) deletion in the sequence encoding the propeptide region of the precursor promyostatin and additional modifier genes of the Compact genetic background contribute to determine the full expression of the phenotype. In this study, by using mice strains carrying mutant or wild-type myostatin alleles with Compact genetic background, and non-mutant myostatin with wild-type background we studied separately the effect of the Mstn(Cmpt-dl1Abc) mutation or the Compact genetic background on morphology, metabolism and signaling...
December 13, 2016: American Journal of Physiology. Endocrinology and Metabolism
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