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American Journal of Physiology. Endocrinology and Metabolism

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https://www.readbyqxmd.com/read/28811296/a-novel-d2o-tracer-method-to-quantify-rna-turnover-as-a-biomarker-of-de-novo-ribosomal-biogenesis-in-vitro-in-animal-models-and-in-human-skeletal-muscle
#1
Matthew S Brook, Daniel J Wilkinson, W Kyle Mitchell, Jonathan L Lund, Bethan E Phillips, Nathaniel J Sweczyk, Heikki Kainulainen, Sanna Lensu, Lauren G Koch, Steve L Britton, Paul L Greenhaff, Kenneth Smith, Philip J Atherton
Current methods to quantify RNA dynamics are beset with limitations. Here, we developed a novel stable isotope (D2O)-methodology to quantify RNA synthesis (i.e. ribosomal biogenesis) in cells, animal models, and humans. Firstly, proliferating C2C12 cells were incubated in D2O-enriched media and myotubes (±) 50ng.ml(-1) IGF-1. Secondly, rat quadriceps [untrained n=9; 7-wks interval-"like" training n=13] were collected after ~3-wks D2O (70-Atom%) administration, with body-water enrichment (BWE) monitored via blood sampling...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28811295/circulating-soluble-rage-isoforms-are-attenuated-in-obese-impaired-glucose-tolerant-individuals-and-are-associated-with-the-development-of-type-2-diabetes
#2
Edwin R Miranda, Vikram S Somal, Jacob T Mey, Brian K Blackburn, Edward Wang, Sarah S Farabi, Kristian Karstoft, Ciaran E Fealy, Sangeeta R Kashyap, John P Kirwan, Laurie Quinn, Thomas P J Solomon, Jacob M Haus
The soluble receptor for advanced glycation endproducts (sRAGE) may be protective against inflammation associated with obesity and type 2 diabetes (T2DM). The aim of this study was to determine the distribution of sRAGE isoforms, and whether sRAGE isoforms are associated with risk of T2DM development in subjects spanning the glucose tolerance continuum. In this retrospective analysis, circulating total sRAGE and endogenous secretory RAGE (esRAGE) were quantified via ELISA and cleaved RAGE (cRAGE) was calculated in 274 individuals stratified by glucose tolerance status (GTS) and obesity...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28811294/dihydrocapsiate-improved-age-associated-impairments-in-mice-by-increasing-energy-expenditure
#3
Kana Ohyama, Katsuya Suzuki
Metabolic dysfunction is associated with aging and results in age-associated chronic diseases, including type 2 diabetes mellitus, cardiovascular disease, and stroke. Hence, there has been a focus on increasing energy expenditure in aged populations to protect them from age-associated diseases. Dihydrocapsiate (DCT) is a compound that belongs to the capsinoid family. Capsinoids are capsaicin analogs that are found in non-pungent peppers and increase whole-body energy expenditure. However, their effect on energy expenditure has been reported only in young populations, and to date the effectiveness of DCT in increasing energy expenditure in aged populations has not been investigated...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28811293/the-glucagon-like-peptide-1-receptor-in-the-ventromedial-hypothalamus-reduces-short-term-food-intake-in-male-mice-by-regulating-nutrient-sensor-activity
#4
Melissa A Burmeister, Jacob D Brown, Jennifer E Ayala, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the glucagon-like peptide 1 receptor (GLP-1R) in the ventromedial hypothalamus (VMH) reduces food intake. Here, we assessed whether suppression of food intake by GLP-1R agonists (GLP-1RA) in this region is dependent upon AMP-activated protein kinase (AMPK) and mammalian Target of Rapamycin (mTOR). We found that pharmacological inhibition of glycolysis and, thus, activation of AMPK, in the VMH attenuates the anorectic effect of the GLP-1R agonist exendin-4 (Ex4), indicating that glucose metabolism and inhibition of AMPK are both required for this effect...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28811292/dapagliflozin-slows-the-progression-of-the-renal-and-liver-fibrosis-associated-with-type-2-diabetes
#5
Li Tang, Yuanyuan Wu, Mi Tian, C David Sjostrom, Ulrika Johansson, Xiao-Rong Peng, David M Smith, Yufeng Huang
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic oral agents indicating promising effects on cardiovascular and renal end points. However, the renoprotective effects of SGLT2 inhibitors are not fully understood. Also, metabolic effects of SGLT2 inhibition on other organ systems such as effects on hepatic steatosis are not fully understood. This study sought to address these questions by treating 18week-old uninephrectomized db/db mice with a selective SGLT2 inhibitor dapagliflozin...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28790027/increased-mitochondrial-calcium-uniporter-in-adipocytes-underlies-mitochondrial-alterations-associated-with-insulin-resistance
#6
Lauren E Wright, Denis Vecellio Reane, Gabriella Milan, Anna Terrin, Giorgia di Bello, Anna Belligoli, Marta Sanna, Mirto Foletto, Francesca Favaretto, Anna Raffaello, Cristina Mammucari, Donato Nitti, Roberto Vettor, Rosario Rizzuto
Intracellular calcium influences an array of pathways and affects cellular processes. With the rapidly progressing research investigating the molecular identity and the physiological roles of the Mitochondrial Calcium Uniporter (MCU) complex, we now have the tools to understand the functions of mitochondrial Ca(2+) in the regulation of pathophysiological processes. Herein, we describe the role of key MCU complex components in insulin resistance in mouse and human adipose tissue. Adipose tissue gene expression was analysed from several models of obese and diabetic rodents and in obese patients, as well as in vitro insulin-resistant adipocytes...
August 8, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28765273/cross-sex-testosterone-therapy-in-ovariectomized-mice-addition-of-low-dose-estrogen-preserves-bone-architecture
#7
Laura G Goetz, Ramanaiah Mamillapalli, Maureen J Devlin, Amy E Robbins, Masoumeh Majidi-Zolbin, Hugh S Taylor
Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here we investigate the long-term effects of XHT on bone health, using a murine model. Female mice underwent ovariectomy at either 6 or 10 weeks, and began weekly testosterone or vehicle injections. Dual-energy X-ray Absorptiometry (DXA) was performed to measure bone mineral density (BMD) and microCT was performed to compare femoral cortical and trabecular bone architecture...
August 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28765272/-calories-in-calories-out-and-macronutrient-intake-the-hope-hype-and-science-of-calories
#8
Scott Howell, Richard Kones
One of the central tenets in obesity prevention and management is caloric restriction. This perspective presents salient features of how calories and energy balance matter, also called the "calories in, calories out paradigm." Determinants of energy balance and relationships to dietary macronutrient content are reviewed. The rationale and features of the carbohydrate-insulin hypothesis postulate that carbohydrate restriction confers a metabolic advantage. According to this model, a large amount of fat intake is enabled without weight gain...
August 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28765271/sirt6-regulates-metabolic-homeostasis-in-skeletal-muscle-through-activation-of-ampk
#9
Xiaona Cui, Lu Yao, Xiaoying Yang, Yong Gao, Fude Fang, Jun Zhang, Qinghua Wang, Yongsheng Chang
Due to the mass and functions in metabolism, skeletal muscle is one of major organs regulating whole-body metabolic homeostasis. SIRT6, a histone deacetylase, has been shown to regulate metabolism in liver and brain, however, its specific role in skeletal muscle is undetermined. In the present study we explored physiological function of SIRT6 in muscle. We generated a muscle-specific SIRT6 knockout mouse model. The mice with SIRT6 deficiency in muscle displayed impaired glucose homeostasis and insulin sensitivity, attenuated whole-body energy expenditure and weakened exercise performance...
August 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28743757/lipid-droplet-size-and-location-in-human-skeletal-muscle-fibers-are-associated-with-insulin-sensitivity
#10
Joachim Nielsen, Anders E Christensen, Birgitte Nellemann, Britt Christensen
In skeletal muscle, an accumulation of lipid droplets (LDs) in the subsarcolemmal space is associated with insulin resistance, but the underlying mechanism is not clear. We aimed to investigate how the size, number and location of LDs are associated with insulin sensitivity and muscle fiber types, and are regulated by aerobic training and treatment with an erythropoiesis-stimulating agent (ESA) in healthy young untrained males. LD analyses were performed by quantitative transmission electron microscopy and insulin sensitivity was assessed by a hyperinsulinemic euglycemic clamp...
July 25, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28720584/protein-kinase-n2-regulates-amp-kinase-signaling-and-insulin-responsiveness-of-glucose-metabolism-in-skeletal-muscle
#11
Maxwell A Ruby, Isabelle Riedl, Julie Massart, Marcus Åhlin, Juleen R Zierath
Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. As skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. While Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo...
July 18, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28720583/central-effects-of-insulin-detemir-on-feeding-body-weight-and-metabolism-in-rats
#12
Joseph R Vasselli, F Xavier Pi-Sunyer, Daniel G Wall, Catherine S John, Colin D Chapman, Paul J Currie
Insulin detemir (DET) is a basal insulin analog that, in contrast to other long-acting forms of insulin, has significant weight-gain sparing effects in diabetic patients. We hypothesized that this effect of DET may be due to its enhanced catabolic action in the CNS. We investigated the long-term effects of single third ventricular (3V) microinjections of equimolar doses of DET and regular insulin in normal male rats on feeding, body weight, energy expenditure (EE) and respiratory quotient (RQ). Also in acute testing, we assessed the ability of lower doses of DET to alter feeding, EE and RQ when microinjected directly into the paraventricular nucleus (PVN)...
July 18, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28698283/long-term-rates-of-mitochondrial-protein-synthesis-are-increased-in-mouse-skeletal-muscle-with-high-fat-feeding-regardless-of-insulin-sensitizing-treatment
#13
Sean A Newsom, Benjamin F Miller, Karyn L Hamilton, Sarah E Ehrlicher, Harrison D Stierwalt, Matthew M Robinson
Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet, the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle...
July 11, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28698282/circulating-sex-steroids-co-regulate-adipose-tissue-immune-cell-populations-in-healthy-men
#14
Katya B Rubinow, Jing Chao, Derek Hagman, Mario Kratz, Brian Van Yserloo, Nilesh W Gaikwad, John K Amory, Stephanie T Page
Male hypogonadism results in changes in body composition characterized by increases in fat mass. Resident immune cells influence energy metabolism in adipose tissue and could promote increased adiposity through paracrine effects. We hypothesized that manipulation of circulating sex steroid levels in healthy men would alter adipose tissue immune cell populations. Subjects (n=44 men, 19-55 years of age) received 4 weeks of treatment with the GnRH receptor antagonist acyline with daily administration of 1) placebo gel, 2) 1...
July 11, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28698281/mir-27b-augments-bone-marrow-progenitor-cell-survival-via-suppressing-the-mitochondrial-apoptotic-pathway-in-type-2-diabetes
#15
Hainan Li, Jenney Liu, Yihan Wang, Zhiyao Fu, Maik Huttemann, Terrence J Monks, Alex F Chen, Jie-Mei Wang
INTRODUCTION: Bone marrow derived progenitor cells (BMPCs) are potential candidates for autologous cell therapy in tissue repair because of their high angiogenic potential. However, increased progenitor cell apoptosis in diabetes directly limits their success in the clinic. MicroRNAs are endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level, but their roles in BMPC-mediated angiogenesis are incompletely understood. In the present study, we tested the hypothesis that the pro-angiogenic miR-27b inhibits BMPC apoptosis in type 2 diabetes...
July 11, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28698280/glycemic-control-after-metabolic-surgery-a-granger-causality-and-graph-analysis
#16
Elena Previti, Serenella Salinari, Alessandro Bertuzzi, Esmeralda Capristo, Stefan Bornstein, Geltrude Mingrone
To examine the contribution of Non-Esterified Fatty-Acids (NEFA) and incretin to insulin-resistance and diabetes amelioration after malabsorptive metabolic-surgery that dramatically reduces circulating NEFA. In fact, NEFA infusion reduces glucose-stimulated insulin secretion and high-fat diets predict diabetes development. Six healthy-controls, 11 obese and 10 Type-2-Diabetic (T2D) subjects were studied before and 1 month after Bilio-Pancreatic Diversion (BPD). Twenty-four hours plasma glucose, NEFA, insulin, C-peptide, glucagon-like peptide-1 (GLP1) and gastric-inhibitory-polypeptide (GIP) time courses were obtained and analyzed by Granger causality and graph analyses...
July 11, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28679626/the-bradykinin-bk-cgmp-pkg-pathway-augments-insulin-sensitivity-via-upregulation-of-mapk-phosphatase-5-and-inhibition-of-jun-kinase-jnk
#17
Maria E Frigolet, Garry Thomas, Kristin Beard, Huogen Lu, Lijiang Liu, I George Fantus
Bradykinin (BK) promotes insulin sensitivity and glucose uptake in adipocytes and other cell types. We demonstrated that in rat adipocytes BK enhances insulin-stimulated glucose transport via endothelial nitric oxide synthase (eNOS), nitric oxide (NO) generation, and decreased activity of the mitogen activated protein kinase (MAPK), JNK (c-Jun-N-terminal kinase). In endothelial cells, NO increases soluble guanylate cyclase (sGC) activity which in turn, activates protein kinase G (PKG) by increasing cGMP levels...
July 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28679625/adaptive-facultative-diet-induced-thermogenesis-in-wild-type-but-not-in-ucp1-ablated-mice
#18
Gabriella von Essen, Erik Lindsund, Barbara Cannon, Jan Nedergaard
The significance of diet-induced thermogenesis (DIT) for metabolic control is still debated. Although obesogenic diets recruit UCP1 and adrenergically inducible thermogenesis, and although the absence of UCP1 may promote the development of obesity, no actual UCP1-related thermogenesis identifiable as diet-induced thermogenesis has to date been unambiguously demonstrated. Examining mice living at thermoneutrality, we have identified a process of facultative (directly elicited by acute eating), adaptive (magnitude develops over weeks on an obesogenic diet) and fully UCP1-dependent thermogenesis...
July 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28679624/factors-regulating-subcutaneous-adipose-tissue-storage-fibrosis-and-inflammation-may-underlie-low-fatty-acid-mobilization-in-insulin-sensitive-obese-adults
#19
Douglas W Van Pelt, Lisa M Guth, Abigail Y Wang, Jeffrey F Horowitz
Although the rate of fatty acid release from adipose tissue into the systemic circulation is very high in most obese adults, some obese adults maintain relatively low rates of fatty acid release, which helps protect them against the development of systemic insulin resistance. The primary aim of this study was to identify factors in adipose tissue that may underlie low vs. high rates of fatty acid mobilization in a relatively homogeneous cohort of obese adults. We measured systemic fatty acid rate of appearance (FA Ra) via (13)C-palmitate isotope dilution, and we obtained subcutaneous abdominal adipose tissue samples from 30 obese adults (BMI: 38±1 kg/m(2), age: 30±2 yr) after an overnight fast...
July 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28679623/high-but-not-low-exercise-volume-shifts-the-balance-of-renin-angiotensin-system-towards-ace2-mas-receptor-axis-in-skeletal-muscle-in-obese-rats
#20
Eliete Dalla Corte Frantz, Isabele Gomes Giori, Marcus Vinícius Machado, D'Angelo Carlo Magliano, Fernanda Marques Freitas, Mariana Sodré Boêta Andrade, Aline Bomfim Vieira, Antonio Claudio Lucas Claudio Lucas da Nóbrega, Eduardo Tibirica
Metabolic Syndrome (MS) is a cluster of metabolic risk factors which is linked to central obesity, elevated blood pressure, insulin resistance (IR) and dyslipidemia, where the rennin-angiotensin system (RAS) may provide a link among them. This study aimed to evaluate volume exercise effects comparing low versus high volume of chronic aerobic exercise on RAS axes in skeletal muscle in a diet-induced obesity (DIO) rat model. For this, male Wistar-Kyoto rats were fed a standard chow diet (SC) or a high-fat diet (HF) for 32 weeks...
July 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
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