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https://www.readbyqxmd.com/read/27473038/metabolomic-profiling-identifies-novel-circulating-biomarkers-of-mitochondrial-dysfunction-differentially-elevated-in-heart-failure-with-preserved-versus-reduced-ejection-fraction-evidence-for-shared-metabolic-impairments-in-clinical-heart-failure
#1
Wynn G Hunter, Jacob P Kelly, Robert W McGarrah, Michel G Khouri, Damian Craig, Carol Haynes, Olga Ilkayeva, Robert D Stevens, James R Bain, Michael J Muehlbauer, Christopher B Newgard, G Michael Felker, Adrian F Hernandez, Eric J Velazquez, William E Kraus, Svati H Shah
BACKGROUND: Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We identified HFpEF cases, HFrEF controls, and no-HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization...
2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27408778/branched-chain-amino-acid-restriction-in-zucker-fatty-rats-improves-muscle-insulin-sensitivity-by-enhancing-efficiency-of-fatty-acid-oxidation-and-acyl-glycine-export
#2
Phillip J White, Amanda L Lapworth, Jie An, Liping Wang, Robert W McGarrah, Robert D Stevens, Olga Ilkayeva, Tabitha George, Michael J Muehlbauer, James R Bain, Jeff K Trimmer, M Julia Brosnan, Timothy P Rolph, Christopher B Newgard
OBJECTIVE: A branched-chain amino acid (BCAA)-related metabolic signature is strongly associated with insulin resistance and predictive of incident diabetes and intervention outcomes. To better understand the role that this metabolite cluster plays in obesity-related metabolic dysfunction, we studied the impact of BCAA restriction in a rodent model of obesity in which BCAA metabolism is perturbed in ways that mirror the human condition. METHODS: Zucker-lean rats (ZLR) and Zucker-fatty rats (ZFR) were fed either a custom control, low fat (LF) diet, or an isonitrogenous, isocaloric LF diet in which all three BCAA (Leu, Ile, Val) were reduced by 45% (LF-RES)...
July 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27003444/research-resource-roles-for-calcium-calmodulin-dependent-protein-kinase-kinase-2-camkk2-in-systems-metabolism
#3
Kathrina L Marcelo, Thomas Ribar, Christopher R Means, Anna Tsimelzon, Robert D Stevens, Olga Ilkayeva, James R Bain, Susan G Hilsenbeck, Christopher B Newgard, Anthony R Means, Brian York
A number of epidemiological studies have implicated calcium (Ca(2+)) signaling as a major factor in obesity that contributes to aberrant systems metabolism. Somewhat paradoxically, obesity correlates with decreased circulating Ca(2+) levels, leading to increased release of intracellular Ca(2+) stores from the endoplasmic reticulum. These findings suggest that insulin resistance associated with the obese state is linked to activation of canonical Ca(2+) signaling pathways. Mechanistically, increased intracellular Ca(2+) binds calmodulin (CaM) to activate a set of Ca(2+)/CaM-dependent protein kinases...
May 2016: Molecular Endocrinology
https://www.readbyqxmd.com/read/26254576/impact-of-combined-resistance-and-aerobic-exercise-training-on-branched-chain-amino-acid-turnover-glycine-metabolism-and-insulin-sensitivity-in-overweight-humans
#4
Erin L Glynn, Lucy W Piner, Kim M Huffman, Cris A Slentz, Lorraine Elliot-Penry, Hiba AbouAssi, Phillip J White, James R Bain, Michael J Muehlbauer, Olga R Ilkayeva, Robert D Stevens, Kathryn N Porter Starr, Connie W Bales, Elena Volpi, M Julia Brosnan, Jeff K Trimmer, Timothy P Rolph, Christopher B Newgard, William E Kraus
AIMS/HYPOTHESES: Obesity is associated with decreased insulin sensitivity (IS) and elevated plasma branched-chain amino acids (BCAAs). The purpose of this study was to investigate the relationship between BCAA metabolism and IS in overweight (OW) individuals during exercise intervention. METHODS: Whole-body leucine turnover, IS by hyperinsulinaemic-euglycaemic clamp, and circulating and skeletal muscle amino acids, branched-chain α-keto acids and acylcarnitines were measured in ten healthy controls (Control) and nine OW, untrained, insulin-resistant individuals (OW-Untrained)...
October 2015: Diabetologia
https://www.readbyqxmd.com/read/26242235/murf2-regulates-ppar%C3%AE-1-activity-to-protect-against-diabetic-cardiomyopathy-and-enhance-weight-gain-induced-by-a-high-fat-diet
#5
Jun He, Megan T Quintana, Jenyth Sullivan, Traci L Parry, Trisha J Grevengoed, Jonathan C Schisler, Joseph A Hill, Cecelia C Yates, Rudo F Mapanga, M Faadiel Essop, William E Stansfield, James R Bain, Christopher B Newgard, Michael J Muehlbauer, Yipin Han, Brian A Clarke, Monte S Willis
BACKGROUND: In diabetes mellitus the morbidity and mortality of cardiovascular disease is increased and represents an important independent mechanism by which heart disease is exacerbated. The pathogenesis of diabetic cardiomyopathy involves the enhanced activation of PPAR transcription factors, including PPARα, and to a lesser degree PPARβ and PPARγ1. How these transcription factors are regulated in the heart is largely unknown. Recent studies have described post-translational ubiquitination of PPARs as ways in which PPAR activity is inhibited in cancer...
2015: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/26220149/algorithm-that-delivers-an-individualized-rapid-acting-insulin-dose-after-morning-resistance-exercise-counters-post-exercise-hyperglycaemia-in-people-with-type-1-diabetes
#6
D Turner, S Luzio, B J Gray, S C Bain, S Hanley, A Richards, D C Rhydderch, R Martin, M D Campbell, L P Kilduff, D J West, R M Bracken
AIMS: To develop an algorithm that delivers an individualized dose of rapid-acting insulin after morning resistance exercise to counter post-exercise hyperglycaemia in individuals with Type 1 diabetes. METHODS: Eight people with Type 1 diabetes, aged 34 ± 7 years with HbA1c concentrations 72 ± 12 mmol/mol (8.7 ± 1.1%), attended our laboratory on two separate mornings after fasting, having taken their usual basal insulin the previous evening. These people performed a resistance exercise session comprising six exercises for two sets of 10 repetitions at 60% of the maximum amount of force that was generated in one maximal contraction (60% 1RM)...
April 2016: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/26215257/muscle-ring-finger-3-protects-against-diabetic-cardiomyopathy-induced-by-a-high-fat-diet
#7
Megan T Quintana, Jun He, Jenyth Sullivan, Trisha Grevengoed, Jonathan Schisler, Yipin Han, Joseph A Hill, Cecelia C Yates, William E Stansfield, Rudo F Mapanga, M Faadiel Essop, Michael J Muehlbauer, Christopher B Newgard, James R Bain, Monte S Willis
BACKGROUND: The pathogenesis of diabetic cardiomyopathy (DCM) involves the enhanced activation of peroxisome proliferator activating receptor (PPAR) transcription factors, including the most prominent isoform in the heart, PPARα. In cancer cells and adipocytes, post-translational modification of PPARs have been identified, including ligand-dependent degradation of PPARs by specific ubiquitin ligases. However, the regulation of PPARs in cardiomyocytes and heart have not previously been identified...
July 28, 2015: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/25919405/similar-magnitude-of-post-exercise-hyperglycemia-despite-manipulating-resistance-exercise-intensity-in-type-1-diabetes-individuals
#8
D Turner, B J Gray, S Luzio, G Dunseath, S C Bain, S Hanley, A Richards, D C Rhydderch, M Ayles, L P Kilduff, M D Campbell, D J West, R M Bracken
The aim of this study was to compare the glycemic and glucoregulatory hormone responses to low- and moderate-intensity morning resistance exercise (RE) sessions in type 1 diabetes (T1DM). Following maximal strength assessments (1RM), eight T1DM (HbA1C :72 ± 12 mmol/mol, age:34 ± 7 years, body mass index:25.7 ± 1.6 kg/m(2) ) participants attended the research facility on two separate occasions, having fasted and taken their usual basal insulin but omitting rapid-acting insulin. Participants performed six exercises for two sets of 20 repetitions at 30%1RM during one session [low-intensity RE session (LOW)] and two sets of 10 repetitions at 60%1RM during another session [moderate-intensity RE session (MOD)], followed by 65-min recovery...
April 2016: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/25874237/changes-in-plasma-levels-of-n-arachidonoyl-ethanolamine-and-n-palmitoylethanolamine-following-bariatric-surgery-in-morbidly-obese-females-with-impaired-glucose-homeostasis
#9
Akhila Mallipedhi, Sarah L Prior, Gareth Dunseath, Richard M Bracken, Jonathan Barry, Scott Caplin, Nia Eyre, James Morgan, John N Baxter, Saoirse E O'Sullivan, Sarir Sarmad, David A Barrett, Stephen C Bain, Steve D Luzio, Jeffrey W Stephens
AIM: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. METHODS: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). RESULTS: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively...
2015: Journal of Diabetes Research
https://www.readbyqxmd.com/read/25202817/sex-differences-in-biomarkers-associated-with-insulin-resistance-in-obese-adolescents-metabolomic-profiling-and-principal-components-analysis
#10
Dorothee Newbern, Pinar Gumus Balikcioglu, Metin Balikcioglu, James Bain, Michael Muehlbauer, Robert Stevens, Olga Ilkayeva, Diana Dolinsky, Sarah Armstrong, Krystal Irizarry, Michael Freemark
OBJECTIVE: Obesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as biomarkers or determinants of IR in obese teens. RESEARCH DESIGN AND METHODS: Fasting blood samples were analyzed by tandem mass spectrometry in 82 obese adolescents. A principal components analysis and multiple linear regression models were used to correlate metabolic components with surrogate measures of IR: homeostasis model assessment index of insulin resistance (HOMA-IR), adiponectin, and triglyceride (TG) to high-density lipoprotein (HDL) ratio...
December 2014: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/24955982/adp-ribosylation-factor-6-regulates-endothelin-1-induced-lipolysis-in-adipocytes
#11
Jonathon C B Davies, Stephen C Bain, Venkateswarlu Kanamarlapudi
Endothelin-1 (ET-1) induces lipolysis in adipocytes, where ET-1 chronic exposure results in insulin resistance (IR) through suppression of glucose transporter (GLUT)4 translocation to the plasma membrane and consequently glucose uptake. ARF6 small GTPase, which plays a vital role in cell surface receptors trafficking, has previously been shown to regulate GLUT4 recycling and thereby insulin signalling. ARF6 also plays a role in ET-1 promoted endothelial cell migration. However, ARF6 involvement in ET-1-induced lipolysis in adipocytes is unknown...
August 15, 2014: Biochemical Pharmacology
https://www.readbyqxmd.com/read/24702172/reductions-in-resistance-exercise-induced-hyperglycaemic-episodes-are-associated-with-circulating-interleukin-6-in-type-1-diabetes
#12
RANDOMIZED CONTROLLED TRIAL
D Turner, S Luzio, L P Kilduff, B J Gray, G Dunseath, S C Bain, M D Campbell, D J West, R M Bracken
AIMS: To determine the influence of different volumes of resistance exercise on circulating interleukin-6 (IL-6) and to explore the relationships between IL-6 and glycaemia. METHODS: Eight participants with complication-free type 1 diabetes, whose mean ± SEM age was 38 (6) years, mean ± SEM HbA(1c) concentration was 71 ±11 mmol/mol (8.7 ±1.0%) and mean ± SEM type 1 diabetes duration was 15 ±13 years, attended the research facility after an overnight fast on four separate occasions, having administered their basal insulin the night before (glargine 27...
August 2014: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/24646137/impact-of-single-and-multiple-sets-of-resistance-exercise-in-type-1-diabetes
#13
D Turner, S Luzio, B J Gray, G Dunseath, E D Rees, L P Kilduff, M D Campbell, D J West, S C Bain, R M Bracken
To examine glycemic and glucoregulatory responses to resistance exercise (RE) sessions of different volume in type 1 diabetes (T1DM). Eight T1DM (seven males: one female; age: 38 ± 6 years, HbA1C : 8.7 ± 1.0%/71 ± 11 mmol/mol) attended the research facility fasted and on four separate occasions, having taken their usual basal insulin, but omitted morning rapid-acting insulin. Participants completed a 1SET (14 min), 2SET (28 min), 3SET (42 min) RE session (eight exercises × 10 repetitions) at 67 ± 3% one-repetition-maximum followed by 60-min recovery, or a resting trial (CON)...
February 2015: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/24401236/validation-of-the-association-between-a-branched-chain-amino-acid-metabolite-profile-and-extremes-of-coronary-artery-disease-in-patients-referred-for-cardiac-catheterization
#14
Sayanti Bhattacharya, Christopher B Granger, Damian Craig, Carol Haynes, James Bain, Robert D Stevens, Elizabeth R Hauser, Christopher B Newgard, William E Kraus, L Kristin Newby, Svati H Shah
OBJECTIVE: To validate independent associations between branched-chain amino acids (BCAA) and other metabolites with coronary artery disease (CAD). METHODS: We conducted mass-spectrometry-based profiling of 63 metabolites in fasting plasma from 1983 sequential patients undergoing cardiac catheterization. Significant CAD was defined as CADindex ≥ 32 (at least one vessel with ≥ 95% stenosis; N = 995) and no CAD as CADindex ≤ 23 and no previous cardiac events (N = 610)...
January 2014: Atherosclerosis
https://www.readbyqxmd.com/read/23990511/metabolomics-reveals-broad-scale-metabolic-perturbations-in-hyperglycemic-mothers-during-pregnancy
#15
COMPARATIVE STUDY
Denise M Scholtens, Michael J Muehlbauer, Natalie R Daya, Robert D Stevens, Alan R Dyer, Lynn P Lowe, Boyd E Metzger, Christopher B Newgard, James R Bain, William L Lowe
OBJECTIVE To characterize metabolites across the range of maternal glucose by comparing metabolomic profiles of mothers with high and low fasting plasma glucose (FPG). RESEARCH DESIGN AND METHODS We compared fasting serum from an oral glucose tolerance test at ∼28 weeks' gestation from 67 Northern European ancestry mothers from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study with high (>90th percentile) FPG with 50 mothers with low (<10th percentile) FPG but comparable BMI. Metabolic data from biochemical analyses of conventional clinical metabolites, targeted mass spectrometry (MS)-based measurement of amino acids, and nontargeted gas chromatography/MS were subjected to per-metabolite analyses and collective pathway analyses using Unipathway annotation...
2014: Diabetes Care
https://www.readbyqxmd.com/read/23881193/metabolomics-reveals-unexpected-responses-to-oral-glucose
#16
COMMENT
James R Bain, Michael J Muehlbauer
No abstract text is available yet for this article.
August 2013: Diabetes
https://www.readbyqxmd.com/read/23809366/beyond-amyloid-getting-real-about-nonamyloid-targets-in-alzheimer-s-disease
#17
Karl Herrup, Maria C Carrillo, Dale Schenk, Angela Cacace, Susan Desanti, Robert Fremeau, Ratan Bhat, Marcie Glicksman, Patrick May, Russell Swerdlow, Linda J Van Eldik, Lisa J Bain, Samantha Budd
For decades, researchers have focused primarily on a pathway initiated by amyloid beta aggregation, amyloid deposition, and accumulation in the brain as the key mechanism underlying the disease and the most important treatment target. However, evidence increasingly suggests that amyloid is deposited early during the course of disease, even prior to the onset of clinical symptoms. Thus, targeting amyloid in patients with mild to moderate Alzheimer's disease (AD), as past failed clinical trials have done, may be insufficient to halt further disease progression...
July 2013: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/23613559/-prediction-is-very-hard-especially-about-the-future-new-biomarkers-for-type-2-diabetes
#18
COMMENT
William L Lowe, James R Bain
No abstract text is available yet for this article.
May 2013: Diabetes
https://www.readbyqxmd.com/read/23375209/branched-chain-amino-acids-are-novel-biomarkers-for-discrimination-of-metabolic-wellness
#19
RANDOMIZED CONTROLLED TRIAL
Bryan C Batch, Svati H Shah, Christopher B Newgard, Christy B Turer, Carol Haynes, James R Bain, Michael Muehlbauer, Mahesh J Patel, Robert D Stevens, Lawrence J Appel, L Kristin Newby, Laura P Svetkey
OBJECTIVE: To identify novel biomarkers through metabolomic profiles that distinguish metabolically well (MW) from metabolically unwell (MUW) individuals, independent of body mass index (BMI). MATERIALS/METHODS: This study was conducted as part of the Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) project. Individuals from 3 cohorts were classified as lean (BMI<25kg/m²), overweight (BMI≥25kg/m², BMI<30kg/m²) or obese (BMI≥30kg/m²)...
July 2013: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/23238293/a-lipidomics-analysis-of-the-relationship-between-dietary-fatty-acid-composition-and-insulin-sensitivity-in-young-adults
#20
RANDOMIZED CONTROLLED TRIAL
C Lawrence Kien, Janice Y Bunn, Matthew E Poynter, Robert Stevens, James Bain, Olga Ikayeva, Naomi K Fukagawa, Catherine M Champagne, Karen I Crain, Timothy R Koves, Deborah M Muoio
Relative to diets enriched in palmitic acid (PA), diets rich in oleic acid (OA) are associated with reduced risk of type 2 diabetes. To gain insight into mechanisms underlying these observations, we applied comprehensive lipidomic profiling to specimens collected from healthy adults enrolled in a randomized, crossover trial comparing a high-PA diet to a low-PA/high-OA (HOA) diet. Effects on insulin sensitivity (SI) and disposition index (DI) were assessed by intravenous glucose tolerance testing. In women, but not men, SI and DI were higher during HOA...
April 2013: Diabetes
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