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Cardiac insulin signaling

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https://www.readbyqxmd.com/read/29590321/polymorphisms-within-ryr3-gene-are-associated-with-risk-and-age-at-onset-of-hypertension-diabetes-and-alzheimer-s-disease
#1
Shaoqing Gong, Brenda Bin Su, Hugo Tovar, ChunXiang Mao, Valeria Gonzalez, Ying Liu, Yongke Lu, Ke-Sheng Wang, Chun Xu
Background: Hypertension affects 33% of Americans while type 2 diabetes and Alzheimer's disease (AD) affect 10% of Americans, respectively. Ryanodine receptor 3 gene (RYR3) codes for the ryanodine receptor which functions to release stored endoplasmic reticulum calcium ions (Ca2+ ) to increase intracellular Ca2+ concentration. Increasing studies demonstrate that altered levels of intracellular Ca2+ affects cardiac contraction, insulin secretion and neurodegeneration. In this study, we investigated associations of the RYR3 genetic variants with hypertension, AD, and diabetes...
March 26, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29581288/small-proline-rich-protein-2b-drives-stress-dependent-p53-degradation-and-fibroblast-proliferation-in-heart-failure
#2
Ryan M Burke, Janet K Lighthouse, Pearl Quijada, Ronald A Dirkx, Alexander Rosenberg, Christine S Moravec, Jeffrey D Alexis, Eric M Small
Heart disease is associated with the accumulation of resident cardiac fibroblasts (CFs) that secrete extracellular matrix (ECM), leading to the development of pathological fibrosis and heart failure. However, the mechanisms underlying resident CF proliferation remain poorly defined. Here, we report that small proline-rich protein 2b ( Sprr2b ) is among the most up-regulated genes in CFs during heart disease. We demonstrate that SPRR2B is a regulatory subunit of the USP7/MDM2-containing ubiquitination complex...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29577579/hepatic-and-cardiac-beneficial-effects-of-a-long-acting-fc-apelin-fusion-protein-in-diet-induced-obese-mice
#3
Weimin Wang, Dongming Zhang, Rongze Yang, Wei Xia, Kun Qian, Zhengrong Shi, Robert Brown, Huifen Zhou, Yue Xi, Lin Shi, Ling Chen, Feng Xu, Xiaojian Sun, Dalong Zhu, Da-Wei Gong
BACKGROUND: Apelin is a peptide ligand of the G-protein-coupled receptor APJ and exhibits anti-diabetes and anti-heart failure activities. However, short serum half-life of the apelin peptide limits its potential clinical applications. This study aimed to develop a long-acting apelin analog. METHODS: To extend apelin's in vivo half-life, we made a recombinant protein by fusing the IgG Fc fragment to apelin-13 (Fc-apelin-13), conducted pharmacokinetics studies in mice, and determined in vitro biological activities in suppressing cyclic adenosine monophosphate and activating extracellular signal-regulated kinase signalling by reporter assays...
March 25, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29566382/testosterone-deprivation-aggravates-left-ventricular-dysfunction-in-male-obese-insulin-resistant-rats-via-impairing-cardiac-mitochondrial-function-and-dynamics-proteins
#4
Nattayaporn Apaiajai, Titikorn Chunchai, Thidarat Jaiwongkam, Sasiwan Kerdphoo, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: We have previously reported that testosterone deprivation at a very young age accelerated, but did not aggravate, left-ventricular (LV) dysfunction in obese insulin-resistant rats. However, the effects of testosterone deprivation during adulthood on LV function in obese insulin-resistant rats remains unclear. We hypothesized that testosterone deprivation aggravates LV dysfunction and cardiac autonomic imbalance via the impairment of cardiac mitochondrial function and dynamics proteins, a reduction in insulin receptor function, and an increase in apoptosis in obese insulin-resistant rats...
March 22, 2018: Gerontology
https://www.readbyqxmd.com/read/29542814/effects-of-ramelteon-on-cardiac-injury-and-adipose-tissue-pathology-in-rats-with-metabolic-syndrome
#5
Ayako Uchinaka, Yuri Kawashima, Yuki Sano, Shogo Ito, Yusuke Sano, Kai Nagasawa, Natsumi Matsuura, Mamoru Yoneda, Yuichiro Yamada, Toyoaki Murohara, Kohzo Nagata
Melatonin regulates circadian rhythms but also has antioxidative and anti-inflammatory effects that ameliorate metabolic disorders. We investigated the effects of the selective melatonin agonist ramelteon on cardiac and adipose tissue pathology in the DahlS.Z-Leprfa /Leprfa (DS/obese) rat, a model of metabolic syndrome (MetS). Rats were treated with a low (0.3 mg/kg per day) or high (8 mg/kg per day) dose of ramelteon from 9 to 13 weeks of age. Ramelteon treatment at either dose attenuated body weight gain, left ventricular fibrosis, and diastolic dysfunction, as well as cardiac oxidative stress and inflammation, without affecting hypertension or insulin resistance...
March 15, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29484207/cardiac-development-and-transcription-factors-insulin-signalling-insulin-resistance-and-intrauterine-nutritional-programming-of-cardiovascular-disease
#6
REVIEW
Annelene Govindsamy, Strinivasen Naidoo, Marlon E Cerf
Programming with an insult or stimulus during critical developmental life stages shapes metabolic disease through divergent mechanisms. Cardiovascular disease increasingly contributes to global morbidity and mortality, and the heart as an insulin-sensitive organ may become insulin resistant, which manifests as micro- and/or macrovascular complications due to diabetic complications. Cardiogenesis is a sequential process during which the heart develops into a mature organ and is regulated by several cardiac-specific transcription factors...
2018: Journal of Nutrition and Metabolism
https://www.readbyqxmd.com/read/29467020/insulin-like-growth-factor-1-mediated-regulation-of-mir-193a-expression-promotes-the-migration-and-proliferation-of-c-kit-positive-mouse-cardiac-stem-cells
#7
Yuning Sun, Rongfeng Xu, Jia Huang, Yuyu Yao, Xiaodong Pan, Zhongpu Chen, Genshan Ma
BACKGROUND: C-kit-positive cardiac stem cells (CSCs) have been shown to be a promising candidate treatment for myocardial infarction and heart failure. Insulin-like growth factor (IGF)-1 is an anabolic growth hormone that regulates cellular proliferation, differentiation, senescence, and death in various tissues. Although IGF-1 promotes the migration and proliferation of c-kit-positive mouse CSCs, the underlying mechanism remains unclear. METHODS: Cells were isolated from adult mouse hearts, and c-kit-positive CSCs were separated using magnetic beads...
February 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29449364/diabetic-cardiomyopathy-an-update-of-mechanisms-contributing-to-this-clinical-entity
#8
REVIEW
Guanghong Jia, Michael A Hill, James R Sowers
Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy...
February 16, 2018: Circulation Research
https://www.readbyqxmd.com/read/29437011/involvement-of-pi3k-akt-and-rhoa-in-oestradiol-regulation-of-cardiac-inos-expression
#9
Sonja Zafirovic, Emina Sudar-Milovanovic, Milan Obradovic, Jelena Djordjevic, Nebojsa Jasnic, Milica Labudovic Borovic, Esma R Isenovic
BACKGROUND: Oestradiol is an important regulatory factor with several positive effects on the cardiovascular (CV) system. We evaluated the molecular mechanism of the in vivo effects of oestradiol on the regulation of cardiac inducible nitric oxide (NO) synthase (iNOS) expression and activity. METHODS: Male Wistar rats were treated with oestradiol (40 mg/kg, intraperitoneally) and after 24 h the animals were sacrificed. The concentrations of NO and L-Arginine (L-Arg) were determined spectrophotometrically...
February 12, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29424246/increased-plasma-fgf21-level-as-an-early-biomarker-for-insulin-resistance-and-metabolic-disturbance-in-obese-insulin-resistant-rats
#10
Pongpan Tanajak, Wanpitak Pongkan, Siriporn C Chattipakorn, Nipon Chattipakorn
Propose: To investigate the temporal relationship between plasma fibroblast growth factor 21 levels, insulin resistance, metabolic dysfunction and cardiac fibroblast growth factor 21 resistance in long-term high-fat diet-induced obese rats. METHODS: In total, 36 male Wistar rats were fed with either a normal diet or high-fat diet for 12 weeks. Blood was collected from the tail tip, and plasma was used to determine metabolic profiles and fibroblast growth factor 21 levels. Rats were sacrificed at weeks 4, 8 and 12, and the hearts were rapidly removed for the determination of cardiac fibroblast growth factor 21 signalling pathways...
February 1, 2018: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/29424033/mitochondrial-dysfunction-in-human-skeletal-muscle-biopsies-of-lipid-storage-disorder
#11
B Debashree, Manish Kumar, T S Keshava Prasad, Archana Natarajan, Rita Christopher, A Nalini, P S Bindu, N Gayathri, M M Srinivas Bharath
Mitochondria regulate the balance between lipid metabolism and storage in the skeletal muscle. Altered lipid transport, metabolism and storage influence the bioenergetics, redox status and insulin signalling contributing to cardiac and neurological diseases. Lipid storage disorders (LSDs) are neurological disorders which entail intramuscular lipid accumulation and impaired mitochondrial bioenergetics in the skeletal muscle causing progressive myopathy with muscle weakness. However, the mitochondrial changes including molecular events associated with impaired lipid storage have not been completely understood in the human skeletal muscle...
February 9, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29396368/liver-specific-rescuing-of-ceacam1-reverses-endothelial-and-cardiovascular-abnormalities-in-male-mice-with-null-deletion-of-ceacam1-gene
#12
Lucia Russo, Harrison T Muturi, Hilda E Ghadieh, Alexander M Wisniewski, Eric E Morgan, Syed S Quadri, Gavin P Landesberg, Helmy M Siragy, Guillermo Vazquez, Rosario Scalia, Rajesh Gupta, Sonia M Najjar
OBJECTIVE: Mice with global null mutation of Ceacam1 (Cc1-/-), display impairment of insulin clearance that causes hyperinsulinemia followed by insulin resistance, elevated hepatic de novo lipogenesis, and visceral obesity. In addition, they manifest abnormal vascular permeability and elevated blood pressure. Liver-specific rescuing of Ceacam1 reversed all of the metabolic abnormalities in Cc1-/-liver+ mice. The current study examined whether Cc1-/- male mice develop endothelial and cardiac dysfunction and whether this relates to the metabolic abnormalities caused by defective insulin extraction...
January 26, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29392420/cardioprotective-effect-of-ghrelin-against-myocardial-infarction-induced-left-ventricular-injury-via-inhibition-of-socs3-and-activation-of-jak2-stat3-signaling
#13
Refaat A Eid, Mahmoud A Alkhateeb, Samy Eleawa, Fahaid H Al-Hashem, Mubarak Al-Shraim, Attalla Farag El-Kott, Mohamed Samir Ahmed Zaki, Mohammad A Dallak, Hussain Aldera
The molecular mechanisms through which ghrelin exerts its cardioprotective effects during cardiac remodeling post-myocardial infarction (MI) are poorly understood. The aim of this study was to investigate whether the cardioprotection mechanisms are mediated by modulation of JAK/STAT signaling and what triggers this modulation. Rats were divided into six groups (n = 12/group): control, sham, sham + ghrelin (100 µg/kg, s.c., daily, starting 1 day post-MI), MI, MI+ ghrelin, and MI+ ghrelin+ AG490, a potent JAK2 inhibitor (5 mg/kg, i...
February 1, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29378301/connexin43-and-zonula-occludens-1-are-targets-of-akt-in-cardiomyocytes-that-correlate-with-cardiac-contractile-dysfunction-in-akt-deficient-hearts
#14
Sangmi Ock, Wang Soo Lee, Hyun Min Kim, Kyu-Sang Park, Young-Kook Kim, Hyun Kook, Woo Jin Park, Tae Jin Lee, E D Abel, Jaetaek Kim
While deletion of Akt1 results in a smaller heart size and Akt2-/- mice are mildly insulin resistant, Akt1-/-/Akt2-/- mice exhibit perinatal lethality, indicating a large degree of functional overlap between the isoforms of the serine/threonine kinase Akt. The present study aimed to determine the cooperative contribution of Akt1 and Akt2 on the structure and contractile function of adult hearts. To generate an inducible, cardiomyocyte-restricted Akt2 knockout (KO) model, Akt2flox/flox mice were crossed with tamoxifen-inducible MerCreMer transgenic (MCM) mice and germline Akt1-/- mice to generate the following genotypes:Akt1+/+; Akt2flox/flox (WT), Akt2flox/flox; α-MHC-MCM (iAkt2 KO), Akt1-/-, and Akt1-/-; Akt2flox/flox; α-MHC-MCM mice (Akt1-/-/iAkt2 KO)...
January 31, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29377150/cardioprotective-effects-of-dietary-rapamycin-on-adult-female-c57blks-j-lepr-db-mice
#15
Peter C Reifsnyder, Sergey Ryzhov, Kevin Flurkey, Rea P Anunciado-Koza, Ian Mills, David E Harrison, Robert A Koza
Rapamycin (RAPA), an inhibitor of mTORC signaling, has been shown to extend life span in mice and other organisms. Recently, animal and human studies have suggested that inhibition of mTORC signaling can alleviate or prevent the development of cardiomyopathy. In view of this, we used a murine model of type 2 diabetes (T2D), BKS-Leprdb , to determine whether RAPA treatment can mitigate the development of T2D-induced cardiomyopathy in adult mice. Female BKS-Leprdb mice fed diet supplemented with RAPA from 11 to 27 weeks of age showed reduced weight gain and significant reductions of fat and lean mass compared with untreated mice...
January 29, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29332196/bioelectronic-modulation-of-carotid-sinus-nerve-activity-in-the-rat-a-potential-therapeutic-approach-for-type-2-diabetes
#16
Joana F Sacramento, Daniel J Chew, Bernardete F Melo, Matteo Donegá, Wesley Dopson, Maria P Guarino, Alison Robinson, Jesus Prieto-Lloret, Sonal Patel, Bradley J Holinski, Nishan Ramnarain, Victor Pikov, Kristoffer Famm, Silvia V Conde
AIMS/HYPOTHESIS: A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function...
March 2018: Diabetologia
https://www.readbyqxmd.com/read/29328372/differential-microrna-expression-profiles-and-bioinformatics-analysis-between-young-and-aging-spontaneously-hypertensive-rats
#17
Jingfeng Wang, Jingjing Zhang, Xuefeng Ding, Yanyan Wang, Zhiming Li, Weipeng Zhao, Jianguo Jia, Jingmin Zhou, Junbo Ge
MicroRNAs (miRNAs/miRs) serve a role as important regulators in cardiac hypertrophy. The present study aimed to reveal the differential expression profile of miRNAs between young and aging spontaneously hypertensive rats (SHRs) and studied the functional annotation of predicted targets. Briefly, 3‑month‑old and 12‑month‑old SHRs (n=3/group) were subjected to echocardiography, histopathological analysis and dihydroethidium staining. Subsequently, small RNA sequencing and data processing was conducted to identify the differentially expressed miRNAs between these two groups...
March 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29277329/human-embryonic-stem-cell-derived-cardiomyocytes-as-an-in-vitro-model-to-study-cardiac-insulin-resistance
#18
Ilvy M E Geraets, Dipanjan Chanda, Florence H J van Tienen, Arthur van den Wijngaard, Rick Kamps, Dietbert Neumann, Yilin Liu, Jan F C Glatz, Joost J F P Luiken, Miranda Nabben
Patients with type 2 diabetes (T2D) and/or insulin resistance (IR) have an increased risk for the development of heart failure (HF). Evidence indicates that this increased risk is linked to an altered cardiac substrate preference of the insulin resistant heart, which shifts from a balanced utilization of glucose and long-chain fatty acids (FAs) towards an almost complete reliance on FAs as main fuel source. This shift leads to a loss of endosomal proton pump activity and increased cardiac fat accumulation, which eventually triggers cardiac dysfunction...
December 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29236751/lysophosphatidic-acid-receptor-mrna-levels-in-heart-and-white-adipose-tissue-are-associated-with-obesity-in-mice-and-humans
#19
Amy Brown, Intekhab Hossain, Lester J Perez, Carine Nzirorera, Kathleen Tozer, Kenneth D'Souza, Purvi C Trivedi, Christie Aguiar, Alexandra M Yip, Jennifer Shea, Keith R Brunt, Jean-Francois Legare, Ansar Hassan, Thomas Pulinilkunnil, Petra C Kienesberger
BACKGROUND: Lysophosphatidic acid (LPA) receptor signaling has been implicated in cardiovascular and obesity-related metabolic disease. However, the distribution and regulation of LPA receptors in the myocardium and adipose tissue remain unclear. OBJECTIVES: This study aimed to characterize the mRNA expression of LPA receptors (LPA1-6) in the murine and human myocardium and adipose tissue, and its regulation in response to obesity. METHODS: LPA receptor mRNA levels were determined by qPCR in i) heart ventricles, isolated cardiomyocytes, and perigonadal adipose tissue from chow or high fat-high sucrose (HFHS)-fed male C57BL/6 mice, ii) 3T3-L1 adipocytes and HL-1 cardiomyocytes under conditions mimicking gluco/lipotoxicity, and iii) human atrial and subcutaneous adipose tissue from non-obese, pre-obese, and obese cardiac surgery patients...
2017: PloS One
https://www.readbyqxmd.com/read/29217479/distinct-lipidomic-profiles-in-models-of-physiological-and-pathological-cardiac-remodeling-and-potential-therapeutic-strategies
#20
Yow Keat Tham, Kevin Huynh, Natalie A Mellett, Darren C Henstridge, Helen Kiriazis, Jenny Y Y Ooi, Aya Matsumoto, Natalie L Patterson, Junichi Sadoshima, Peter J Meikle, Julie R McMullen
Cardiac myocyte membranes contain lipids which remodel dramatically in response to heart growth and remodeling. Lipid species have both structural and functional roles. Physiological and pathological cardiac remodeling have very distinct phenotypes, and the identification of molecular differences represent avenues for therapeutic interventions. Whether the abundance of specific lipid classes is different in physiological and pathological models was largely unknown. The aim of this study was to determine whether distinct lipids are regulated in settings of physiological and pathological remodeling, and if so, whether modulation of differentially regulated lipids could modulate heart size and function...
March 2018: Biochimica et Biophysica Acta
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