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Meghan G Patton, Trevor L Gillum, Mandy C Szymanski, Lacey M Gould, Claire J Lauterbach, Roger A Vaughan, Matthew R Kuennen
This work investigated the effect of a 6-day heat acclimation (HA) protocol on myotube metabolic responses at baseline and in response to a subsequent lipopolysaccharide (LPS) challenge. C2C12 myotubes were incubated for 2 h/day at 40 °C for 6 days (HA) or maintained at 37 °C (C). Following 24-h recovery, myotubes were challenged with 500 ng/ml LPS for 2 h, then collected for analysis of protein markers of mitochondrial biogenesis and macronutrient storage. Functional significance of these changes was confirmed with mitochondrial respiration and glycolytic measurements on a Seahorse XF-96 analyzer...
April 11, 2018: Cell Stress & Chaperones
Agnieszka Polak, Ewa Harasim-Symbor, Barbara Malinowska, Irena Kasacka, Alicja Lewandowska, Adrian Chabowski
BACKGROUND/AIMS: Recent interest in the use of cannabinoids as therapeutic agents has revealed the involvement of the endogenous cannabinoid system (ECS) in the regulation of the cardiovascular system in hypertension. Abnormalities in glucose metabolism and insulin action are commonly detected in hypertensive animals. Thus, potential antihypertensive drugs should be investigated with respect to modulation of glucose homeostasis. Therefore, the aim of the present study was to evaluate the effects of the ECS activation after chronic fatty acid amide hydrolase inhibitor (URB597) administration on plasma glucose and insulin concentrations as well as parameters of myocardial glucose metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rats, an animal model of secondary hypertension...
March 29, 2018: Cellular Physiology and Biochemistry
Jia Qi, Wangsheng Wang, Qinling Zhu, Yaqiong He, Yao Lu, Yuan Wang, Xiaoxue Li, Zi-Jiang Chen, Yun Sun
Context: Endometrial insulin resistance may account for the endometrial dysfunction in polycystic ovary syndrome (PCOS). The underlying mechanism remains to be elucidated. Objective: To investigate whether the abundance of 11β-hydroxysteroid dehydrogenases (11β-HSD1 and -2) and cortisol as well as the insulin signaling pathway are altered in PCOS endometrium and to clarify the relationship between endometrial insulin resistance (IR) and local cortisol. Design: We measured cortisol and cortisone concentrations, 11β-HSD1 and -2, and core insulin signaling molecules in endometrial biopsies collected from non-PCOS and PCOS with or without IR patients on day hCG+7...
March 30, 2018: Journal of Clinical Endocrinology and Metabolism
Rajiv Gandhi Sathiyabama, Gopalsamy Rajiv Gandhi, Marina Denadai, Gurunagarajan Sridharan, Gnanasekaran Jothi, Ponnusamy Sasikumar, Jullyana de Souza Siqueira Quintans, Narendra Narain, Luis Eduardo Cuevas, Henrique Douglas Melo Coutinho, Andreza Guedes Barbosa Ramos, Lucindo José Quintans-Júnior, Ricardo Queiroz Gurgel
Citrus sinensis (L.) Osbeck is extensively cultivated worldwide and one of the most consumed fruits in the world. We evaluated the therapeutic properties of the methanol extract from Citrus sinensis fruit peel (CSMe) in high-fat diet-fed streptozotocin-induced insulin-resistant diabetic rats. Body weight, food intake, and water consumption were analysed. Biochemical and molecular biologic indices, and the expression of insulin receptor-induced signalling molecules were assessed to identify possible mechanisms...
April 1, 2018: Food and Chemical Toxicology
Patrícia Ebersbach-Silva, Ana Cláudia Poletto, Aline David-Silva, Patrícia Monteiro Seraphim, Gabriel Forato Anhê, Marisa Passarelli, Daniela Tomie Furuya, Ubiratan Fabres Machado
BACKGROUND: Obesity is strongly associated to insulin resistance, inflammation, and elevated plasma free fatty acids, but the mechanisms behind this association are not fully comprehended. Evidences suggest that endoplasmic reticulum (ER) stress may play a role in this complex pathophysiology. The aim of the present study was to investigate the involvement of inflammation and ER stress in the modulation of glucose transporter GLUT4, encoded by Slc2a4 gene, in L6 skeletal muscle cells...
April 2, 2018: Lipids in Health and Disease
Srivani Telapolu, Mangathayaru Kalachavedu, Alan Mathew Punnoose, Dwarakanath Bilikere
BACKGROUND: Type 2 Diabetes (T2D) is a polygenic disease requiring a multipronged therapeutic approach. In the current scenario, the use of polyherbals is increasing among the diabetics. MD-1, a poly herbal formulation is constituted as a mixture of six popular anti diabetic herbs, used in the management of Diabetes mellitus (DM). The physicochemical, biochemical and in vitro efficacy studies have been carried out to ascertain the possible mechanisms underlying the anti-diabetic action of MD-1...
April 2, 2018: BMC Complementary and Alternative Medicine
Pascal Gottmann, Meriem Ouni, Sophie Sausenthaler, Julian Roos, Laura Stirm, Markus Jähnert, Anne Kamitz, Nicole Hallahan, Wenke Jonas, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger, Matthias Blüher, Pamela Fischer-Posovszky, Heike Vogel, Annette Schürmann
OBJECTIVE: Obesity and type 2 diabetes (T2D) arise from the interplay between genetic, epigenetic, and environmental factors. The aim of this study was to combine bioinformatics and functional studies to identify miRNAs that contribute to obesity and T2D. METHODS: A computational framework (miR-QTL-Scan) was applied by combining QTL, miRNA prediction, and transcriptomics in order to enhance the power for the discovery of miRNAs as regulative elements. Expression of several miRNAs was analyzed in human adipose tissue and blood cells and miR-31 was manipulated in a human fat cell line...
March 15, 2018: Molecular Metabolism
Jung-Hak Kim, Sun-Ji Park, Unbin Chae, Joongbae Seong, Hyun-Shik Lee, Sang-Rae Lee, Seunghoon Lee, Dong-Seok Lee
Insulin signaling is essential for regulating glucose homeostasis. Numerous studies have demonstrated that reactive oxygen species (ROS) affect insulin signaling, and low ROS levels can act as a signal to regulate cellular function. Peroxiredoxins (Prxs) are highly abundant and widely expressed antioxidant enzymes. However, it is unclear whether antioxidant enzymes, such as Prx2, mediate insulin signaling. The aim of our study was to investigate the influence of Prx2 deficiency on insulin signaling. Our western blot results showed that Prx2 deficiency enhanced insulin signaling and increased oxidation of protein tyrosine phosphatase 1B (PTP1B) and phosphatase and tensin homologue (PTEN) in mouse embryonic fibroblasts (MEFs) treated with insulin...
March 29, 2018: International Journal of Biochemistry & Cell Biology
Francisco Les, José Miguel Arbonés-Mainar, Marta Sofía Valero, Víctor López
ETHNOPHARMACOLOGICAL RELEVANCE: pomegranate fruit is considered an antidiabetic medicine in certain systems of traditional medicine. In addition, pomegranate polyphenols are known as powerful antioxidants with beneficial effects such as the reduction of oxidative / inflammatory stress and the increase of protective signalling such as antioxidant enzymes, neurotrophic factors and cytoprotective proteins. AIM OF THE STUDY: this work evaluates the effects of pomegranate juice, its main polyphenols known as ellagic acid and punicalagin, as well as its main metabolite urolithin A, on physiological and pharmacological targets of metabolic diseases such as obesity and diabetes...
March 28, 2018: Journal of Ethnopharmacology
Daniel J Fazakerley, Annabel Y Minard, James R Krycer, Kristen C Thomas, Jacqueline Stöckli, Dylan J Harney, James G Burchfield, Ghassan J Maghzal, Stuart T Caldwell, Richard C Hartley, Roland Stocker, Michael P Murphy, David E James
Mitochondrial oxidative stress, mitochondrial dysfunction, or both have been implicated in insulin resistance. However, disentangling the individual roles of these processes in insulin resistance has been difficult since they often occur in tandem and tools that selectively increase oxidant production without impairing mitochondrial respiration have been lacking. Using the dimer:monomer status of peroxiredoxin isoforms as an indicator of compartmental hydrogen peroxide burden, we provide evidence that oxidative stress is localized to mitochondria in insulin resistant 3T3-L1 adipocytes and adipose tissue from mice...
March 29, 2018: Journal of Biological Chemistry
Gregory Alexander Raciti, Francesca Fiory, Michele Campitelli, Antonella Desiderio, Rosa Spinelli, Michele Longo, Cecilia Nigro, Giacomo Pepe, Eduardo Sommella, Pietro Campiglia, Pietro Formisano, Francesco Beguinot, Claudia Miele
Metabolic and/or endocrine dysfunction of the white adipose tissue (WAT) contribute to the development of metabolic disorders, such as Type 2 Diabetes (T2D). Therefore, the identification of products able to improve adipose tissue function represents a valuable strategy for the prevention and/or treatment of T2D. In the current study, we investigated the potential effects of dry extracts obtained from Citrus aurantium L. fruit juice (CAde) on the regulation of 3T3-L1 cells adipocyte differentiation and function in vitro...
2018: PloS One
Lili Zhu, Xiaoyun Zhu, Guibo Sun, Xiangbao Meng, Min Wang, Hanming Cui, Jialong Wang, Yadong Zhai, Ke Yang, Yang Tang, Xiaobo Sun, Ximing Liu
Intricate health problems, such as insulin resistance (IR) and its associated diseases, call for multi-targeted therapies with few side effects. Based on traditional Chinese medicine (TCM), Dai-Zong-Fang (DZF) is an herbal formula mainly composed of Rhizoma Coptidis (Huanglian) and Fructus Aurantii Immaturus (Zhishi), of which berberine and naringin are the main constituents. Though DZF has been clinically used for treatment of IR and metabolic syndrome for decades, its mechanism in vivo remains unknown. In the present study, we observed that both DZF and metformin, the first-line drug for type 2 diabetes, ameliorated insulin resistance with significant improvement of oral glucose tolerance test (OGTT) and homeostasis model assessment of IR (HOMA-IR) level in diabetic C57BL/Ksj-Lepr db -/- ( db/db ) mice...
2018: Frontiers in Physiology
Xi Wei, Hua Wei, Dawei Yang, Dong Li, Xianli Yang, Mingjie He, Erbing Lin, Biaoliang Wu
The effects of aluminum (Al) exposure on glucose metabolism and its mechanism were investigated. A total of 30 healthy Wistar male rats were randomly divided into two groups: control (GC) and experimental (GE). The GC group received intraperitoneal normal saline. The GE was established by intraperitoneal injected AlCl3 solution at 10 mg/kg for 30 days. Fasting blood glucose (FBG) and serum levels of insulin (FINS) were measured. The insulin resistance index (HOMA-IR) and pancreatic β cell function index (HOMA-β) were calculated and analyzed with homeostasis model assessment (HOMA)...
March 28, 2018: Biological Trace Element Research
Anik Boudreau, Scott Fuller, David M Ribnicky, Allison J Richard, Jacqueline M Stephens
An ethanolic extract of Baccharis halimifolia (groundsel bush, GB), which is a native Louisiana plant with documented use in Creole folk medicine, has been shown to inhibit lipopolysaccharide (LPS)-induced inflammation in cultured macrophages. Here, we examine the effects of GB on adipocyte development and function, as these processes are attractive targets for intervention in insulin resistance. Oil Red O neutral lipid staining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunoblotting were used to measure GB effects on lipid accumulation, gene expression, and protein abundance, respectively...
March 25, 2018: Biology
Nava Zaarur, Xiang Pan, Konstantin V Kandror
Our ability to explore protein-protein interactions is the key to understanding regulatory connections in the cell. However, detection of protein-protein interactions in many cases is associated with significant experimental challenges. In particular, sorting receptors interact with their protein cargo in the lumen of the membrane compartments often in a detergent-sensitive fashion, making co-immunoprecipitation of these proteins unusable. Binding of the sorting receptor sortilin to glucose transporter GLUT4 may serve as an example of weak luminal interactions between membrane proteins...
March 7, 2018: Journal of Visualized Experiments: JoVE
Veronica Valli, Katharina Heilmann, Francesca Danesi, Alessandra Bordoni, Clarissa Gerhäuser
Obesity is characterized by excess body fat accumulation due to an increase in the size and number of differentiated mature adipocytes. Adipocyte differentiation is regulated by genetic and environmental factors, and its inhibition could represent a strategy for obesity prevention and treatment. The current study was designed with two aims: (i) to evaluate the changes in the expression of adipogenic markers (C/EBP α , PPAR γ variant 1 and variant 2, and GLUT4) in 3T3-L1 murine preadipocytes at four stages of the differentiation process and (ii) to compare the effectiveness of sulforaphane, genistein, and docosahexaenoic acid in reducing lipid accumulation and modulating C/EBP α , PPAR γ 1, PPAR γ 2, and GLUT4 mRNA expression in mature adipocytes...
2018: Oxidative Medicine and Cellular Longevity
Gabriela M Soares, Lucas Zangerolamo, Elis G Azevedo, Jose M Costa-Júnior, Everardo M Carneiro, Sara T Saad, Antonio C Boschero, Helena C Barbosa-Sampaio
GTPase activating proteins (GAPs) are ubiquitously expressed, and their role in cellular adhesion and membrane traffic processes have been well described. TBC1D1, which is a Rab-GAP, is necessary for adequate glucose uptake by muscle cells, whereas increased TCGAP, which is a Rho-GAP, decreases GLUT4 translocation, and consequently glucose uptake in adipocytes. Here, we assessed the possible involvement of ARHGAP21, a Rho-GAP protein, in glucose homeostasis. For this purpose, wild type mice and ARHGAP21 transgenic whole-body gene-deficiency mice (heterozygous mice, expressing approximately 50% of ARHGAP21) were fed either chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD)...
March 25, 2018: Journal of Cellular Physiology
Limei Liu, Ying Wang, Jian Wang, Yunzhou Dong, Scarlett Chang, Xiwen Liu, Kabirullah Lutfy, Hong Chen, Theodore C Friedman, Meisheng Jiang, Yanjun Liu
BACKGROUND: Visceral fat accumulation increases the risk of developing type 2 diabetes and metabolic syndrome, and is associated with excessive glucocorticoids (GCs). Fat depot-specific GC action is tightly controlled by 11ß-hydroxysteroid dehydrogenase (11ß-HSD1) coupled with the enzyme hexose-6-phosphate dehydrogenase (H6PDH). Mice with inactivation or activation of H6PDH genes show altered adipose 11ß-HSD1 activity and lipid storage. We hypothesized that adipose tissue H6PDH activation is a leading cause for the visceral obesity and insulin resistance...
February 22, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Toshiaki Nakajima, Seiichiro Koide, Tomohiro Yasuda, Takaaki Hasegawa, Tatsuya Yamasoba, Syotaro Obi, Shigeru Toyoda, Fumitaka Nakamura, Teruo Inoue, David C Poole, Yutaka Kano
Low force exercise training with blood flow restriction (BFR) elicits muscle hypertrophy. We investigated the effects of microvascular hypoxia (i.e., low microvascular O2 partial pressures, PmvO2 ) during contractions on hypertrophic signaling, growth response and key muscle adaptations for increasing exercise capacity. Wistar rats were fitted with a cuff placed around the upper thigh and inflated to restrict limb blood flow. Low force isometric contractions (30 Hz) were evoked via electrical stimulation of the tibialis anterior (TA) nerve...
March 22, 2018: Journal of Applied Physiology
Sifan Chen, Zhongliang Zhao, Liangru Ke, Zilun Li, Wenxue Li, Zili Zhang, Ying Zhou, Xiang Feng, Wei Zhu
Insulin resistance serves as "common soil" for promoting the development of metabolic diseases; however, the precise pathological factors leading to insulin resistance are not well clarified. Resveratrol (Res) is a natural polyphenolic compound with anti-inflammatory and antioxidative effects. However, effects and mechanisms of Res on glucose metabolism in adipocytes remain largely unknown. In this study, we show Res treatment significantly increases glucose uptake in insulin-resistant 3T3-L1 adipocytes in vitro...
February 13, 2018: Journal of Nutritional Biochemistry
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