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Insulin signaling heart

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)...
October 12, 2016: Diabetologia
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
Aude Belliard, Gaurav K Gulati, Qiming Duan, Rosana Alves, Shannon Brewer, Namrata Madan, Yoann Sottejeau, Xiaoliang Wang, Jennifer Kalisz, Sandrine V Pierre
Cardiac glycosides (CG) are traditionally known as positive cardiac inotropes that inhibit Na(+)/K(+)-ATPase-dependent ion transport. CG also trigger-specific signaling pathways through the cardiac Na(+)/K(+)-ATPase, with beneficial effects in ischemia/reperfusion (I/R) injury (e.g., ouabain preconditioning, known as OPC) and hypertrophy. Our current understanding of hypersensitivity to CG and subsequent toxicity in the ischemic heart is mostly based on specific I/R-induced alterations of the Na(+)/K(+)-ATPase enzymatic function and has remained incomplete...
October 2016: Physiological Reports
U Smith, B B Kahn
Obesity, the major cause of the current global epidemic of type 2 diabetes (T2D), induces insulin resistance in peripheral insulin target tissues. Several mechanisms have been identified related to cross-talk between adipose tissue, skeletal muscle and liver. These mechanisms involve both increased free fatty acid release and altered secretion of adipokines from adipose tissue. A major determinant of metabolic health is the ability of subcutaneous adipose tissue (SAT) to store excess fat rather than allowing it to accumulate in ectopic depots including liver (i...
October 3, 2016: Journal of Internal Medicine
Xiaoshuai Huang, Sun-Hye Bae, Tsvetan R Bachvaroff, Eric J Schott, Haihui Ye, J Sook Chung
Insulin-like peptides (ILPs) have regulatory roles in reproduction, development and metabolism in invertebrates. The mode of ILP actions has not been well studied in invertebrates in regard to the role of binding partners, i.e., ILP binding protein (ILPBP). In this study, the full-length cDNA of Callinectes sapidus ILPBP (Cas-ILPBP, 960 bp) has been isolated using RACE cloning, having short 5' and 3' UTRs of 30 and 162 bp, respectively. The predicted precursor of Cas-ILPBP (255 aa) contains, in order a signal peptide (23 aa), an insulin-like growth factor (IGF) binding (IB) domain (79 aa), a kazal-type serine protease inhibitor (KI) domain (36 aa) and an immunoglobulin (Ig) domain (101 aa)...
September 21, 2016: Fish & Shellfish Immunology
Ha Ram Bae, Dae Hyun Kim, Min Hi Park, Bonggi Lee, Min Jo Kim, Eun Kyeong Lee, Ki Wung Chung, Seong Min Kim, Dong Soon Im, Hae Young Chung
β-Hydroxybutyrate, a ketone body that is used as an energy source in organs such as the brain, muscle, and heart when blood glucose is low, is produced by fatty acid oxidation in the liver under the fasting state. Endoplasmic reticulum (ER) stress is linked with the generation of intracellular reactive oxygen species and the accumulation of misfolded protein in the ER. ER stress is known to induce the NOD-like receptor protein 3 inflammasome, which mediates activation of the proinflammatory cytokine interleukin-1β, whose maturation is caspase-1-dependent...
September 19, 2016: Oncotarget
Jiahe Xie, Kai Cui, Huixin Hao, Yingxue Zhang, Hairuo Lin, Zhenhuan Chen, Xiaobo Huang, Shiping Cao, Wangjun Liao, Jianping Bin, Masafumi Kitakaze, Yulin Liao
BACKGROUND: Left ventricular (LV) dysfunction is closely associated with LV hypertrophy or diabetes, as well as insufficient autophagic flux. Acute or chronic hyperglycemia is a prognostic factor for patients with myocardial infarction. However, the effect of acute hyperglycemia on LV dysfunction of the hypertrophic heart and the mechanisms involved are still unclear. This study aimed to confirm our hypothesis that either acute or chronic hyperglycemia suppresses LV diastolic function and autophagic flux...
2016: Cardiovascular Diabetology
Li Tao, Linna Jia, Yuntian Li, Chengyun Song, Zheng Chen
Heart diseases are major causes of mortality. Cardiac hypertrophy, myocardial infarction (MI), viral cardiomyopathy, ischemic and reperfusion (I/R) heart injury finally lead to heart failure and death. Insulin and IGF1 signal pathways play key roles in normal cardiomyocyte growth and physiological cardiac hypertrophy while inflammatory signal pathway is associated with pathological cardiac hypertrophy, MI, viral cardiomyopathy, I/R heart injury, and heart failure. Adapter proteins are the major family proteins, which transduce signals from insulin, IGF1, or cytokine receptors to the downstream pathways and have been shown to regulate variety of heart diseases...
September 13, 2016: Heart Failure Reviews
Sorabh Sharma, Rajeev Taliyan
Insulin resistance is a common feature of obesity and predisposes the affected individuals to a variety of pathologies, including type 2 diabetes mellitus (T2DM), dyslipidemias, hypertension, cardiovascular disease etc. Insulin resistance is the primary cause of T2DM and it occurs many years before the disease onset. Although Thiazolidinediones (TZDs) such as rosiglitazone and pioglitazone are outstanding insulin sensitizers and are in clinical use since 1990s, however, their serious side effects such as heart attack and bladder cancer have limited their utilization...
September 9, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Paul M Rindler, Angela Cacciola, Michael Kinter, Luke I Szweda
We have recently demonstrated that catalase content in mouse cardiac mitochondria is selectively elevated in response to high dietary fat, a nutritional state associated with oxidative stress and loss in insulin signaling. Catalase and various isoforms of glutathione peroxidase and peroxiredoxin each catalyze the consumption of H2O2 Catalase, located primarily within peroxisomes and to a lesser extent mitochondria, has a low binding affinity for H2O2 relative to glutathione peroxidase and peroxiredoxin. As such, the contribution of catalase to mitochondrial H2O2 consumption is not well understood...
September 9, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Yang Liu, Wenbo Fu, Mu Lu, Shitao Huai, Yaqin Song, Yutao Wei
Background. Epicardial adipose tissue (EAT) is identified as an atypical fat depot surrounding the heart with a putative role in the involvement of metabolic disorders, including obesity, type-2 diabetes mellitus, and atherosclerosis. We profiled miRNAs in EAT of metabolic patients with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) versus metabolically healthy patients by microarray. Compared to metabolically healthy patients, we identified forty-two miRNAs that are differentially expressed in patients with CAD and T2DM from Xinjiang, China...
2016: BioMed Research International
Pierre-Alain Thiebaut, Marie Besnier, Elodie Gomez, Vincent Richard
Protein Tyrosine Phosphatase 1B (PTP1B) is mostly involved in negative regulation of signaling mediated by Tyrosine Kinase Receptors, especially the insulin and leptin receptors. This enzyme thus plays a major role in the development of diseases associated with insulin resistance, such as obesity and diabetes. PTP1B inhibition is currently considered as an attractive treatment of insulin resistance and associated metabolic disorders. In parallel, emerging evidence also suggests that PTP1B is widely expressed in cardiovascular tissues, notably in the heart and the endothelium, and that it could also be a potential treatment of several cardiovascular diseases...
September 2, 2016: Journal of Molecular and Cellular Cardiology
Wail Nammas, Juhani K E Airaksinen, Tuomas Paana, Pasi P Karjalainen
Afferent renal sympathetic nerve signaling regulates central sympathetic outflow. In this regard, renal sympathetic denervation has emerged as a novel interventional strategy for treatment of patients with resistant hypertension. Despite the disappointing results of the Simplicity HTN-3 randomized controlled trial, promoters of renal denervation argue that the negative results were due to ineffective denervation technique and poor patient selection. Yet, long-term "pathologic" increase of efferent sympathetic nerve activity is observed in many chronic disease states characterized by sympathetic overactivity, such as arrhythmia, heart failure, insulin resistance, and chronic kidney disease...
August 30, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Yan Zhang, Hong-Kun Wu, Feng-Xiang Lv, Rui-Ping Xiao
Mitsugumin 53 (MG53), also named Trim72, is a multi-functional TRIM-family protein, which is abundantly expressed in cardiac and skeletal muscle. It has been shown that MG53 not only plays important physiological roles but also acts as a crucial pathogenic factor of various diseases. First, MG53 preserves cardiac and skeletal muscle integrity via facilitating plasma membrane repair. Second, MG53 is essentially involved in cardiac ischemic preconditioning and postconditioning by activating PI3K-Akt-GSK3β and ERK1/2 cell survival signaling pathways...
August 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Anja Hofmann, Coy Brunssen, Mirko Peitzsch, Melanie Martin, Jennifer Mittag, Anett Jannasch, Felix Engelmann, Nicholas F Brown, Steven M Weldon, Jochen Huber, Rüdiger Streicher, Andreas Deussen, Graeme Eisenhofer, Stefan R Bornstein, Henning Morawietz
Plasma aldosterone is elevated in type 2 diabetes and obesity in experimental and clinical studies and can act to inhibit both glucose-stimulated insulin secretion by the β-cell and insulin signaling. Currently mineralocorticoid receptor antagonism is the best characterized treatment to ameliorate aldosterone-mediated effects. A second alternative is inhibition of aldosterone synthase, an approach with protective effects on end-organ damage in heart or kidney in animal models. The effect of aldosterone synthase inhibition on metabolic parameters in type 2 diabetes is not known...
October 2016: Endocrinology
Rui Liu, Justin W Kenney, Antigoni Manousopoulou, Harvey E Johnston, Makoto Kamei, Christopher H Woelk, Jianling Xie, Michael Schwarzer, Spiros D Garbis, Christopher G Proud
Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. In the former, myocardial growth is a risk factor for cardiac failure and faster protein synthesis is a major factor driving cardiomyocyte growth. Our goal was to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are caused by alterations on mRNA abundance or the translation of specific mRNAs. Cardiomyocytes have very low rates of protein synthesis, posing a challenging problem in terms of studying changes in the synthesis of specific proteins, which also applies to other nondividing primary cells...
October 2016: Molecular & Cellular Proteomics: MCP
Mei Wang, Yongjun Li, Kun Zhou, Guoru Zhang, Yaling Wang, Tao Liu, Yang Zhang, Anjun Guo, Yu An
BACKGROUND/AIMS: Extensive research has explored the role of aldosterone in insulin resistance. Recent evidence suggests that the mineralocorticoid receptor (MR) mediates aldosterone-induced dysregulation of cytokines, and most of this research has focused on adjustments in fat tissue and adipocytes. However, the direct effect of MR blockade on insulin resistance in cardiomyocytes remains largely unknown. In the present study, we investigated whether MR blockade improves insulin-sensitizing factors in insulin-resistant rats and attenuates the dysregulation of the aldosterone-related transport of adiponectin and glucose in cardiomyocytes and examined the underlying mechanisms...
2016: Cellular Physiology and Biochemistry
Márta Sárközy, Gergő Szűcs, Veronika Fekete, Márton Pipicz, Katalin Éder, Renáta Gáspár, Andrea Sója, Judit Pipis, Péter Ferdinandy, Csaba Csonka, Tamás Csont
BACKGROUND: There is a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM) due to the worldwide obesity epidemic. However, a significant proportion of T2DM patients are non-obese and they also have an increased risk of cardiovascular diseases. As the Goto-Kakizaki (GK) rat is a well-known model of non-obese T2DM, the goal of this study was to investigate the effect of non-obese T2DM on cardiac alterations of the transcriptome in GK rats. METHODS: Fasting blood glucose, serum insulin and cholesterol levels were measured at 7, 11, and 15 weeks of age in male GK and control rats...
2016: Cardiovascular Diabetology
Elisa Benetti, Raffaella Mastrocola, Giovanna Vitarelli, Juan Carlos Cutrin, Debora Nigro, Fausto Chiazza, Eric Mayoux, Massimo Collino, Roberto Fantozzi
The aim of this study was to evaluate the effects of chronic treatment with empagliflozin, a potent and selective sodium glucose cotransporter-2 inhibitor, in a murine model of diet-induced obesity and insulin resistance, focusing on drug effects on body weight reduction and nucleotide-binding domain, leucine-rich repeat containing protein (NLRP)-3 inflammasome activation, which have never been investigated to date. Male C57BL/6 mice were fed control or a high fat-high sugar (HFHS) diet for 4 months. Over the last 2 months, subsets of animals were treated with empagliflozin (1-10 mg/kg) added to the diet...
October 2016: Journal of Pharmacology and Experimental Therapeutics
Almudena Gómez-Hernández, Nuria Beneit, Óscar Escribano, Sabela Díaz-Castroverde, Gema García-Gómez, Silvia Fernández, Manuel Benito
Obesity is one of the major risk factors for the development of cardiovascular diseases and is characterized by abnormal accumulation of adipose tissue, including perivascular adipose tissue (PVAT). However, brown adipose tissue (BAT) activation reduces visceral adiposity. To demonstrate that severe brown fat lipoatrophy might accelerate atherosclerotic process, we generated a new mouse model without insulin receptor (IR) in BAT and without apolipoprotein (Apo)E (BAT-specific IR knockout [BATIRKO];ApoE(-/-) mice) and assessed vascular and metabolic alterations associated to obesity...
September 2016: Endocrinology
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