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Cardiac insulin signaling

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https://www.readbyqxmd.com/read/28067313/redundant-functions-of-i-bar-family-members-irsp53-and-irtks-are-essential-for-embryonic-development
#1
Ai Mei Chou, Kai Ping Sem, Wei Jun Lam, Sohail Ahmed, Chin Yan Lim
The insulin receptor substrate of 53 kDa, IRSp53, is an adaptor protein that works with activated GTPases, Cdc42 and Rac, to modulate actin dynamics and generate membrane protrusions in response to cell signaling. Adult mice that lack IRSp53 fail to regulate synaptic plasticity and exhibit hippocampus-associated learning deficiencies. Here, we show that 60% of IRSp53 null embryos die at mid to late gestation, indicating a vital IRSp53 function in embryonic development. We find that IRSp53 KO embryos displayed pleiotropic phenotypes such as developmental delay, oligodactyly and subcutaneous edema, and died of severely impaired cardiac and placental development...
January 9, 2017: Scientific Reports
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
#2
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/27989961/role-of-mineralocorticoid-receptor-activation-in-cardiac-diastolic-dysfunction
#3
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
#4
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/27940566/glucose-regulates-the-intrinsic-inflammatory-response-of-the-heart-to-surgically-induced-hypothermic-ischemic-arrest-and-reperfusion
#5
Ahmed S Bux, Merry L Lindsey, Hernan G Vasquez, Heinrich Taegtmeyer, Romain Harmancey
We investigated the isolated working rat heart as a model to study early transcriptional remodeling induced in the setting of open heart surgery and stress hyperglycemia. Hearts of male Sprague Dawley rats were cold-arrested in Krebs-Henseleit buffer and subjected to 60 minutes normothermic reperfusion in the working mode with buffer supplemented with non-carbohydrate substrates plus glucose (25 mM) or mannitol (25 mM; osmotic control). Gene expression profiles were determined by microarray analysis and compared to that of non-perfused hearts...
December 9, 2016: Physiological Genomics
https://www.readbyqxmd.com/read/27931032/fatty-acid-oxidation-and-its-relation-with-insulin-resistance-and-associated-disorders
#6
Gary D Lopaschuk
Alterations in muscle fatty acid metabolism have been implicated in mediating the severity of insulin resistance. In the insulin resistant heart fatty acids are favored as an energy source over glucose, which is thus associated with increased fatty acid oxidation, and an overall decrease in glycolysis and glucose oxidation. In addition, excessive uptake and beta-oxidation of fatty acids in obesity and diabetes can compromise cardiac function. In animal studies, mice fed a high fat diet (HFD) show cardiac insulin resistance in which the accumulation of intra-myocardial diacylglycerol has been implicated, likely involving parallel signaling pathways...
2016: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/27919304/green-tea-extract-intake-during-lactation-modified-cardiac-macrophage-infiltration-and-amp-activated-protein-kinase-phosphorylation-in-weanling-rats-from-undernourished-mother-during-gestation-and-lactation
#7
E Matsumoto, S Kataoka, Y Mukai, M Sato, S Sato
Maternal dietary restriction is often associated with cardiovascular disease in offspring. The aim of this study was to investigate the effect of green tea extract (GTE) intake during lactation on macrophage infiltration, and activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and serine-threonine kinase Akt (Akt) in the hearts of weanlings exposed to maternal dietary protein restriction. Pregnant Wistar rats were fed control (C) or low-protein diets (LP) throughout gestation. Following delivery, the dams received a control or a GTE-containing control diet during lactation: control diet during gestation and lactation (CC), low-protein diet during gestation and lactation (LPC), low-protein diet during gestation and 0...
December 6, 2016: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/27875248/vildagliptin-and-caloric-restriction-for-cardioprotection-in-pre-diabetic-rats
#8
Pongpan Tanajak, Hiranya Pintana, Natthaphat Siri-Angkul, Juthamas Khamseekaew, Nattayaporn Apaijai, Siriporn C Chattipakorn, Nipon Chattipakorn
Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although calorie restriction (CR) has been shown to be useful in obesity, we hypothesized that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater efficacy than monotherapy in attenuating cardiac dysfunction and metabolic impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n = 6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4 weeks...
February 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/27870972/mek-erk-signaling-is-involved-in-the-role-of-vegf-and-igf1-in-cardiomyocyte-differentiation-of-mouse-adipose-tissue-derived-stromal-cells
#9
Chunhui Wang, Wenhui Liu, Xianning Zhang, Yinghui Wang, Huan Liu, Haifang Li
BACKGROUND: We found that mouse brown adipose tissue-derived stromal cells (BATDCs), but not white adipose tissue-derived stromal cells (WATDCs), could spontaneously differentiate into cardiomyocyte-like cells in a simple culture medium. This study would find out some critical trophic factors that were responsible for such difference in differentiation, and further determine the involved signaling pathway. METHODS AND RESULTS: The cardiomyocyte differentiation capacity of cells was identified by morphological observations, immunofluorescence staining, and evaluation of expression of cardiomyocyte specific markers...
February 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27832814/obesity-induced-cardiac-lipid-accumulation-in-adult-mice-is-modulated-by-g-protein-coupled-receptor-kinase-2-levels
#10
Elisa Lucas, Rocio Vila-Bedmar, Alba C Arcones, Marta Cruces-Sande, Victoria Cachofeiro, Federico Mayor, Cristina Murga
BACKGROUND: The leading cause of death among the obese population is heart failure and stroke prompted by structural and functional changes in the heart. The molecular mechanisms that underlie obesity-related cardiac remodeling are complex, and include hemodynamic and metabolic alterations that ultimately affect the functionality of the myocardium. G protein-coupled receptor kinase 2 (GRK2) is an ubiquitous kinase able to desensitize the active form of several G protein-coupled receptors (GPCR) and is known to play an important role in cardiac GPCR modulation...
November 10, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27825849/nuclear-receptor-retinoid-related-orphan-receptor-%C3%AE-deficiency-exacerbates-high-fat-diet-induced-cardiac-dysfunction-despite-improving-metabolic-abnormality
#11
Yi-Chao Zhao, Long-Wei Xu, Song Ding, Qing-Qi Ji, Nan Lin, Qing He, Ling-Chen Gao, Yuan-Yuan Su, Jun Pu, Ben He
Retinoid-related orphan receptor α (RORα), a member of the metabolic nuclear receptor superfamily, plays a vital regulatory role in circadian rhythm and metabolism. Here, we investigated the role of RORα in high-fat diet (HFD)-induced cardiac impairments and the underlying mechanisms involved. RORα-deficient stagger mice (sg/sg) and wild type (WT) littermates were fed with either standard diet or HFD. At 20weeks after HFD treatment, RORα deficiency resulted in significantly decreased body weight gain, improved dyslipidemia and ameliorated insulin resistance (evaluated by blood biochemical and glucose/insulin tolerance tests) compared with WT control...
November 5, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27815373/inhibiting-insulin-mediated-%C3%AE-2-adrenergic-receptor-activation-prevents-diabetes-associated-cardiac-dysfunction
#12
Qingtong Wang, Yongming Liu, Qin Fu, Bing Xu, Yuan Zhang, Sungjin Kim, Ruensern Tan, Federica Barbagallo, Toni West, Ethan Anderson, Wei Wei, E Dale Abel, Yang K Xiang
BACKGROUND: Type 2 diabetes mellitus (DM) and obesity independently increase the risk of heart failure by incompletely understood mechanisms. We propose that hyperinsulinemia might promote adverse consequences in the hearts of subjects with type-2 DM and obesity. METHODS: High-fat diet feeding was used to induce obesity and DM in wild-type mice or mice lacking β2-adrenergic receptor (β2AR) or β-arrestin2. Wild-type mice fed with high-fat diet were treated with a β-blocker carvedilol or a GRK2 (G-protein-coupled receptor kinase 2) inhibitor...
January 3, 2017: Circulation
https://www.readbyqxmd.com/read/27809308/doxorubicin-attenuates-chip-guarded-hsf1-nuclear-translocation-and-protein-stability-to-trigger-igf-iir-dependent-cardiomyocyte-death
#13
Chih-Yang Huang, Wei-Wen Kuo, Jeng-Fan Lo, Tsung-Jung Ho, Pei-Ying Pai, Shu-Fen Chiang, Pei-Yu Chen, Fu-Jen Tsai, Chang-Hai Tsai, Chih-Yang Huang
Doxorubicin (DOX) is one of the most effective antitumor drugs, but its cardiotoxicity has been a major concern for its use in cancer therapy for decades. Although DOX-induced cardiotoxicity has been investigated, the underlying mechanisms responsible for this cardiotoxicity have not been completely elucidated. Here, we found that the insulin-like growth factor receptor II (IGF-IIR) apoptotic signaling pathway was responsible for DOX-induced cardiotoxicity via proteasome-mediated heat shock transcription factor 1 (HSF1) degradation...
November 3, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27803247/nod1-activation-in-cardiac-fibroblasts-induces-myocardial-fibrosis-in-a-murine-model-of-type-2-diabetes
#14
Almudena Val-Blasco, Patricia Prieto-Chinchilla, Silvia Gonzalez-Ramos, Gemma Benito, María Teresa Vallejo-Cremades, Ivette Pacheco, María Pilar González-Peramato, Noelia Agra, Verónica Terrón, Carmen Delgado, Paloma Martín-Sanz, Lisardo Boscá, María Fernández-Velasco
Cardiac fibrosis and chronic inflammation are common complications in type 2 diabetes mellitus (T2D). Since nucleotide oligomerization-binding domain 1 (NOD1), an innate immune receptor, is involved in the pathogenesis of insulin resistance and diabetes outcomes, we sought to investigate its involvement in cardiac fibrosis. Here we show that selective staining of cardiac fibroblasts from T2D ( db/db;db ) mice exhibit up-regulation and activation of the NOD1 pathway, resulting in enhanced NF-kB and TGF-β signalling...
November 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27803037/opposing-roles-of-wnt-inhibitors-igfbp-4-and-dkk1-in-cardiac-ischemia-by-differential-targeting-of-lrp5-6-and-%C3%AE-catenin
#15
Da Wo, Jinhui Peng, Dan-Ni Ren, Liman Qiu, Jinxiao Chen, Ye Zhu, Yingjing Yan, Hongwei Yan, Jian Wu, En Ma, Tao P Zhong, Yihan Chen, Zhongmin Liu, Shangfeng Liu, Luoquan Ao, Zhenping Liu, Cizhong Jiang, Jun Peng, Yunzeng Zou, Qirong Qian, Weidong Zhu
BACKGROUND: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide, triggering irreversible myocardial cell damage and heart failure. The role of low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) as coreceptors of the Wnt/β-catenin pathway in the adult heart remain unknown. Insulin-like growth factor binding protein 4 and dickkopf-related protein 1 (Dkk1) are 2 secreted LRP5/6 binding proteins that play a crucial role in heart development through preventing Wnt/β-catenin pathway activation...
December 13, 2016: Circulation
https://www.readbyqxmd.com/read/27754030/yia-03-06-ramelteon-attenuates-cardiac-injury-improves-insulin-signaling-in-white-adipose-tissue-and-attenuates-whitening-of-brown-adipose-tissue-in-rats-with-metabolic-syndrome
#16
Ayako Uchinaka, Yuri Kawashima, Yuki Sano, Mamoru Yoneda, Shogo Ito, Yusuke Sano, Kai Nagasawa, Natsumi Matsuura, Yuichiro Yamada, Toyoaki Murohara, Kohzo Nagata
OBJECTIVE: The pineal hormone melatonin, which regulates the body's circadian rhythm, possesses anti-oxidative and anti-inflammatory effects and thereby improves metabolic disorders. Ramelteon is a potent and highly selective agonist of melatonin receptors and attenuates age-associated hypertension and body weight gain in spontaneously hypertensive rats. However, the effects of ramelteon on cardiovascular and metabolic disorders in metabolic syndrome (MetS) remain unclear. We investigated the effects of ramelteon on cardiac and adipose tissue pathology in a rat model of MetS...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753992/ed-05-4-natriuretic-peptides-metabolic-syndrome-and-hypertension-an-integrated-view
#17
Riccardo Sarzani
Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are the cardiac natriuretic peptides (NP), true "cardiometabolic" hormones well known for their renal, endocrine and cardiovascular activities leading to reduced sodium reabsorption and arterial blood pressure. These effects are mainly mediated by the second messenger cGMP that also stimulates lipolysis, mitochondriogenesis and a thermogenic program with potency similar to catecholamines. Two distinct NP receptors modulate the final response to cardiac NP: the cGMP-signaling receptor NPRA and the clearance receptor NPRC...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27734104/effects-of-insulin-induced-hypoglycaemia-on-lipolysis-rate-lipid-oxidation-and-adipose-tissue-signalling-in-human-volunteers-a-randomised-clinical-study
#18
Thomas S Voss, Mikkel H Vendelbo, Ulla Kampmann, Steen B Pedersen, Thomas S Nielsen, Mogens Johannsen, Mads V Svart, Niels Jessen, Niels Møller
AIMS/HYPOTHESIS: The aims of this study were to determine the role of lipolysis in hypoglycaemia and define the underlying intracellular mechanisms. METHODS: Nine healthy volunteers were randomised to treatment order of three different treatments (crossover design). Treatments were: (1) saline control; (2) hyperinsulinaemic hypoglycaemia (HH; i.v. bolus of 0.1 U/kg insulin); and (3) hyperinsulinaemic euglycaemia (HE; i.v. bolus of 0.1 U/kg insulin and 20% glucose)...
January 2017: Diabetologia
https://www.readbyqxmd.com/read/27734035/adipocyte-specific-loss-of-ppar%C3%AE-attenuates-cardiac-hypertrophy
#19
Xi Fang, Matthew J Stroud, Kunfu Ouyang, Li Fang, Jianlin Zhang, Nancy D Dalton, Yusu Gu, Tongbin Wu, Kirk L Peterson, Hsien-Da Huang, Ju Chen, Nanping Wang
Adipose tissue is a key endocrine organ that governs systemic homeostasis. PPARγ is a master regulator of adipose tissue signaling that plays an essential role in insulin sensitivity, making it an important therapeutic target. The selective PPARγ agonist rosiglitazone (RSG) has been used to treat diabetes. However, adverse cardiovascular effects have seriously hindered its clinical application. Experimental models have revealed that PPARγ activation increases cardiac hypertrophy. RSG stimulates cardiac hypertrophy and oxidative stress in cardiomyocyte-specific PPARγ knockout mice, implying that RSG might stimulate cardiac hypertrophy independently of cardiomyocyte PPARγ...
October 6, 2016: JCI Insight
https://www.readbyqxmd.com/read/27708849/highly-purified-eicosapentaenoic-acid-ameliorates-cardiac-injury-and-adipose-tissue-inflammation-in-a-rat-model-of-metabolic-syndrome
#20
S Ito, Y Sano, K Nagasawa, N Matsuura, Y Yamada, A Uchinaka, T Murohara, K Nagata
INTRODUCTION: n-3 Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA), which are abundant in fish oil, have been shown to delay the onset of cardiovascular events. We previously established DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats, as a model of metabolic syndrome. This study has now explored the influence of highly purified EPA on cardiac and adipose tissue pathophysiology in this animal model. MATERIALS AND METHODS: DS/obese rats were administered EPA (300 or 1,000 mg kg(-1) d(-1), per os) or vehicle from age 9 to 13 weeks...
September 2016: Obesity Science & Practice
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