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https://www.readbyqxmd.com/read/29247648/pkc-and-rab13-mediate-ca2-signal-regulated-glut4-traffic
#1
Bangli Deng, Xiaocui Zhu, Yihe Zhao, Da Zhang, Alisha Pannu, Liming Chen, Wenyan Niu
Exercise/muscle contraction increases cell surface glucose transporter 4 (GLUT4), leading to glucose uptake to regulate blood glucose level. Elevating cytosolic Ca2+ mediates this effect, but the detailed mechanism is not clear yet. We used calcium ionophore ionomycin to raise intracellular cytosolic Ca2+ level to explore the underlying mechanism. We showed that in L6 myoblast muscle cells stably expressing GLUT4myc, ionomycin increased cell surface GLUT4myc levels and the phosphorylation of AS160, TBC1D1. siPKCα and siPKCθ but not siPKCδ and siPKCε inhibited the ionomycin-increased cell surface GLUT4myc level...
December 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29247431/infrared-photobiomodulation-pbm-therapy-improves-glucose-metabolism-and-intracellular-insulin-pathway-in-adipose-tissue-of-high-fat-fed-mice
#2
Gabriela Silva, Cleber Ferraresi, Rodrigo Teixeira de Almeida, Mariana Lopes Motta, Thiago Paixão, Vinicius Oliveira Ottone, Ivana Alice Fonseca, Murilo Xavier Oliveira, Etel Rocha-Vieira, Marco Fabrício Dias-Peixoto, Elizabethe Adriana Esteves, Cândido Celso Coimbra, Fabiano Trigueiro Amorim, Flávio de Castro Magalhães
Obesity represents a continuously growing global epidemic and is associated with the development of type 2 diabetes mellitus. The etiology of type 2 diabetes is related to the resistance of insulin-sensitive tissues to its action leading to impaired blood glucose regulation. Photobiomodulation (PBM) therapy might be a non-pharmacological, non-invasive strategy to improve insulin resistance. It has been reported that PBM therapy in combination with physical exercise reduces insulin resistance. Therefore, the aim of this study was to investigate the effects of PBM therapy on insulin resistance in obese mice...
December 15, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/29225317/pre-exercise-high-fat-diet-for-3-days-affects-post-exercise-skeletal-muscle-glycogen-repletion
#3
Yumiko Takahashi, Yutaka Matsunaga, Yuki Tamura, Shin Terada, Hideo Hatta
Previous studies have shown that the short-term intake of a high-fat diet (HFD) impairs glucose metabolism. In this study, we investigated the influences of pre-exercise HFD intake for 3 d on post-exercise glycogen repletion in skeletal muscle in ICR mice. Mice received either an HFD (57% kcal from fat, 23% kcal from carbohydrate; HFD group) or standard laboratory chow (13% kcal from fat, 60% kcal from carbohydrate; Con group) for 3 d before exercise. Mice performed treadmill running at 25 m/min for 60 min and were orally administered a glucose (2 mg/g body weight) solution immediately after and at 60 min after exercise...
2017: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/29204135/recombinant-uncarboxylated-osteocalcin-per-se-enhances-mouse-skeletal-muscle-glucose-uptake-in-both-extensor-digitorum-longus-and-soleus-muscles
#4
Xuzhu Lin, Lewan Parker, Emma Mclennan, Xinmei Zhang, Alan Hayes, Glenn McConell, Tara C Brennan-Speranza, Itamar Levinger
Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK), and/or the mechanistic target of rapamycin complex 2 (mTORC2)-protein kinase B (AKT)-AKT substrate of 160 kDa (AS160) signaling cascade...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29183756/activiated-galanin-receptor-2-attenuates-insulin-resistance-in-skeletal-muscle-of-obese-mice
#5
Penghua Fang, Lei Zhang, Mei Yu, Zhongqi Sheng, Mingyi Shi, Yan Zhu, Zhenwen Zhang, Ping Bo
The results of our and other's studies showed that activation of galanin receptor 1 could mitigate insulin resistance via promoting glucose transporter 4 (GLUT4) expression and translocation in the skeletal muscle of rats. But no literature are available regarding the effect of galanin receptor 2 (GALR2) on insulin resistance in skeletal muscle of type 2 diabetes. Herein, in this study we intended to survey the effect of GALR2 and its signal mechanisms in the mice with high fat diet-induced obese. The mice were intraperitoneally injected with vehicle, GALR2 agonist M1145 and antagonist M871 respectively once a day for continuous 21 days...
November 25, 2017: Peptides
https://www.readbyqxmd.com/read/29177506/lrrk2-phosphorylates-membrane-bound-rabs-and-is-activated-by-gtp-bound-rab7l1-to-promote-recruitment-to-the-trans-golgi-network
#6
Zhiyong Liu, Nicole Bryant, Ravindran Kumaran, Alexandra Beilina, Asa Abeliovich, Mark R Cookson, Andrew B West
Human genetic studies implicate LRRK2 and Rab7L1 in susceptibility to Parkinson disease (PD). These two genes function in the same pathway, as knockout of Rab7L1 results in phenotypes similar to LRRK2 knockout, and studies in cells and model organisms demonstrate LRRK2 and Rab7L1 interact in the endolysosomal system. Recently, a subset of Rab proteins have been identified as LRRK2 kinase substrates. Herein, we find that Rab8, Rab10, and Rab7L1 must be membrane and GTP-bound for LRRK2 phosphorylation. LRRK2 mutations that cause PD including R1441C, Y1699C, and G2019S all increase LRRK2 phosphorylation of Rab7L1 four-fold over wild-type LRRK2 in cells, resulting in the phosphorylation of nearly one-third the available Rab7L1 protein in cells...
November 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29170369/stress-responsive-fkbp51-regulates-akt2-as160-signaling-and-metabolic-function
#7
Georgia Balsevich, Alexander S Häusl, Carola W Meyer, Stoyo Karamihalev, Xixi Feng, Max L Pöhlmann, Carine Dournes, Andres Uribe-Marino, Sara Santarelli, Christiana Labermaier, Kathrin Hafner, Tianqi Mao, Michaela Breitsamer, Marily Theodoropoulou, Christian Namendorf, Manfred Uhr, Marcelo Paez-Pereda, Gerhard Winter, Felix Hausch, Alon Chen, Matthias H Tschöp, Theo Rein, Nils C Gassen, Mathias V Schmidt
The co-chaperone FKBP5 is a stress-responsive protein-regulating stress reactivity, and its genetic variants are associated with T2D related traits and other stress-related disorders. Here we show that FKBP51 plays a role in energy and glucose homeostasis. Fkbp5 knockout (51KO) mice are protected from high-fat diet-induced weight gain, show improved glucose tolerance and increased insulin signaling in skeletal muscle. Chronic treatment with a novel FKBP51 antagonist, SAFit2, recapitulates the effects of FKBP51 deletion on both body weight regulation and glucose tolerance...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29137480/akt-substrate-of-160-kda-dephosphorylation-rate-is-reduced-in-insulin-stimulated-rat-skeletal-muscle-after-acute-exercise
#8
E B Arias, H Wang, G D Cartee
Because greater Akt substrate of 160 kDa (AS160) phosphorylation has been reported in insulin-stimulated skeletal muscles without improved Akt activation several hours post-exercise, we hypothesized that prior exercise would result in attenuated AS160 dephosphorylation in insulin-stimulated rat skeletal muscle. Epitrochlearis muscles were isolated from rats that were sedentary (SED) or exercised 3 h earlier (3 h post-exercise; 3hPEX). Paired muscles were incubated with [(3)H]-2-deoxyglucose (2-DG) without insulin or with insulin...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29089333/electrical-pulse-stimulation-induces-glut4-glucose-transporter-translocation-in-c2c12-myotubes-that-depends-on-rab8a-rab13-and-rab14
#9
Zhu Li, Yingying Yue, Fang Hu, Chang Zhang, Xiaofang Ma, Nana Li, Lihong Qiu, Maolong Fu, Liming Chen, Zhi Yao, Philip J Bilan, Amira Klip, Wenyan Niu
The signals mobilizing GLUT4 to the plasma membrane in response to muscle contraction are less known than those elicited by insulin. This disparity is undoubtedly due to lack of suitable in vitro models to study skeletal muscle contraction. We generated C2C12 myotubes stably expressing HA-tagged GLUT4 (C2C12-GLUT4HA) that contract in response to electrical pulse stimulation (EPS) and investigated molecular mechanisms regulating GLUT4HA EPS (60min, 20V, 1Hz, 24ms pulses at 976ms intervals) elicited a gain in surface GLUT4HA (GLUT4 translocation) comparably to insulin or 5-amino imidazole-4-carboxamide ribonucleotide (AICAR)...
October 31, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28971334/preventive-effect-of-oleate-on-palmitate-induced-insulin-resistance-in-skeletal-muscle-and-its-mechanism-of-action
#10
Hakam Alkhateeb, Esam Qnais
Insulin resistance in skeletal muscle is a feature associated with exposure to an excess of saturated fatty acids such as palmitate. Oleic acid has been shown to blunt palmitate-induced insulin resistance in muscle cells. However, there is no literature available regarding the effect of oleic acid on palmitate-induced insulin resistance in intact muscle. Therefore, this study investigated the effect of oleic acid on palmitate-induced insulin resistance in rat soleus muscle and its underlying mechanisms. For these purposes, oleic acid (1 mM) was administered for 12 h in the absence or presence of palmitate (2 mM)...
November 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28843510/an-alternative-model-for-studying-age-associated-metabolic-complications-senescence-accelerated-mouse-prone-8
#11
Hung-Wen Liu, Yin-Ching Chan, Chu-Chun Wei, Yun-An Chen, Ming-Fu Wang, Sue-Joan Chang
Rodent animal models take at least 18months to develop aging phenotypes for researchers to investigate the mechanism of age-related metabolic complications. Senescence-accelerated mouse prone 8 (SAMP8) shortens the process of aging and may facilitate an alternative model for studying age-related insulin resistance. The short-lived strain SAMP8 and two long-lived strains SAM resistant 1 (SAMR1) mice and C57BL/6 mice at 12 (young) and 40weeks old (old) were used in the present study. Glucose tolerance test, histology and signaling pathways involved in lipid metabolism in adipose tissue and liver and key components of insulin signaling pathway in the skeletal muscle were determined in these three strains...
December 1, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28808062/ablating-the-protein-tbc1d1-impairs-contraction-induced-sarcolemmal-glucose-transporter-4-redistribution-but-not-insulin-mediated-responses-in-rats
#12
Jamie Whitfield, Sabina Paglialunga, Brennan K Smith, Paula M Miotto, Genevieve Simnett, Holly L Robson, Swati S Jain, Eric A F Herbst, Eric M Desjardins, David J Dyck, Lawrence L Spriet, Gregory R Steinberg, Graham P Holloway
TBC1 domain family member 1 (TBC1D1), a Rab GTPase-activating protein and paralogue of Akt substrate of 160 kDa (AS160), has been implicated in both insulin- and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase-mediated glucose transporter type 4 (GLUT4) translocation. However, the role of TBC1D1 in contracting muscle remains ambiguous. We therefore explored the metabolic consequence of ablating TBC1D1 in both resting and contracting skeletal muscles, utilizing a rat TBC1D1 KO model...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28739533/effect-of-bisphenol-a-bpa-on-insulin-signal-transduction-and-glut4-translocation-in-gastrocnemius-muscle-of-adult-male-albino-rat
#13
Vigneswari Mullainadhan, Mangala Priya Viswanathan, Balasubramanian Karundevi
Environmental estrogens bind to estrogen receptors, mimic estrogenic actions, and have adverse effects on human health like Bisphenol - A (BPA) which is used as a monomer in the production of polycarbonate plastics (PC) and epoxy resins which are used in variety of canned foods. Skeletal muscle plays an essential role in maintaining systemic glucose metabolism. In the present study, we investigated the possible effects of BPA on insulin signalling molecules and GLUT4 translocation in the gastrocnemius muscle of adult male rat...
September 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28736261/genetic-disruption-of-the-cardiomyocyte-circadian-clock-differentially-influences-insulin-mediated-processes-in-the-heart
#14
Graham R McGinnis, Yawen Tang, Rachel A Brewer, Manoja K Brahma, Haley L Stanley, Gobinath Shanmugam, Namakkal Soorappan Rajasekaran, Glenn C Rowe, Stuart J Frank, Adam R Wende, E Dale Abel, Heinrich Taegtmeyer, Silvio Litovsky, Victor Darley-Usmar, Jianhua Zhang, John C Chatham, Martin E Young
Cardiovascular physiology exhibits time-of-day-dependent oscillations, which are mediated by both extrinsic (e.g., environment/behavior) and intrinsic (e.g., circadian clock) factors. Disruption of circadian rhythms negatively affects multiple cardiometabolic parameters. Recent studies suggest that the cardiomyocyte circadian clock directly modulates responsiveness of the heart to metabolic stimuli (e.g., fatty acids) and stresses (e.g., ischemia/reperfusion). The aim of this study was to determine whether genetic disruption of the cardiomyocyte circadian clock impacts insulin-regulated pathways in the heart...
September 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28584168/palmitate-and-oleate-exert-differential-effects-on-insulin-signalling-and-glucose-uptake-in-human-skeletal-muscle-cells
#15
Selina Mäkinen, Yen H Nguyen, Paulina Skrobuk, Heikki A Koistinen
Saturated fatty acids are implicated in the development of insulin resistance, whereas unsaturated fatty acids may have a protective effect on metabolism. We tested in primary human myotubes if insulin resistance induced by saturated fatty acid palmitate can be ameliorated by concomitant exposure to unsaturated fatty acid oleate. Primary human myotubes were pretreated with palmitate, oleate or their combination for 12 h. Glucose uptake was determined by intracellular accumulation of [(3)H]-2-deoxy-d-glucose, insulin signalling and activation of endoplasmic reticulum (ER) stress by Western blotting, and mitochondrial reactive oxygen species (ROS) production by fluorescent dye MitoSOX...
July 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28571740/phytol-increases-adipocyte-number-and-glucose-tolerance-through-activation-of-pi3k-akt-signaling-pathway-in-mice-fed-high-fat-and-high-fructose-diet
#16
Jianbing Wang, Xiaoquan Hu, Wei Ai, Fenglin Zhang, Kelin Yang, Lina Wang, Xiaotong Zhu, Ping Gao, Gang Shu, Qingyan Jiang, Songbo Wang
It has been shown that adipose tissue hyperplasia (increased adipocyte number or adipogenesis) has beneficial effects on metabolic health. The aim of the present study was to determine whether phytol could modulate hyperplasia/adipogenesis and glucose homeostasis, and to explore the underlying mechanisms in mice fed high-fat and high fructose diet (HFFD). Our results demonstrated that phytol administration decreased body weight gain and inguinal subcutaneous white adipose tissue (iWAT) weight. However, phytol significantly increased the adipocyte number in iWAT, with the smaller average adipocyte diameter...
August 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28556933/heterotypic-endosomal-fusion-as-an-initial-trigger-for-insulin-induced-glucose-transporter-4-glut4-translocation-in-skeletal-muscle
#17
Hiroyasu Hatakeyama, Makoto Kanzaki
KEY POINTS: Comprehensive imaging analyses of glucose transporter 4 (GLUT4) behaviour in mouse skeletal muscle was conducted. Quantum dot-based single molecule nanometry revealed that GLUT4 molecules in skeletal myofibres are governed by regulatory systems involving 'static retention' and 'stimulus-dependent liberation'. Vital imaging analyses and super-resolution microscopy-based morphometry demonstrated that insulin liberates the GLUT4 molecule from its static state by triggering acute heterotypic endomembrane fusion arising from the very small GLUT4-containing vesicles in skeletal myofibres...
August 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28545963/the-carboxy-terminal-region-of-the-tbc1d4-as160-rabgap-mediates-protein-homodimerization
#18
Ju Rang Woo, Soon-Jong Kim, Keon Young Kim, Hyonchol Jang, Steven E Shoelson, SangYoun Park
TBC1D4 (also known as AS160) is a Rab·GTPase-activating protein (RabGAP) which functions in insulin signaling. TBC1D4 is critical for translocation of glucose transporter 4 (GLUT4), from an inactive, intracellular, vesicle-bound site to the plasma membrane, where it promotes glucose entry into cells. The TBC1D4 protein is structurally subdivided into two N-terminal phosphotyrosine-binding (PTB) domains, a C-terminal catalytic RabGAP domain, and a disordered segment in between containing potential Akt phosphorylation sites...
October 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28522731/effect-of-metformin-on-bioactive-lipid-metabolism-in-insulin-resistant-muscle
#19
Piotr Zabielski, Marta Chacinska, Karol Charkiewicz, Marcin Baranowski, Jan Gorski, Agnieszka U Blachnio-Zabielska
Intramuscular accumulation of bioactive lipids leads to insulin resistance and type 2 diabetes (T2D). There is lack of consensus concerning which of the lipid mediators has the greatest impact on muscle insulin action in vivo Our aim was to elucidate the effects of high-fat diet (HFD) and metformin (Met) on skeletal muscle bioactive lipid accumulation and insulin resistance (IR) in rats. We employed a [U-(13)C]palmitate isotope tracer and mass spectrometry to measure the content and fractional synthesis rate (FSR) of intramuscular long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer)...
June 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28495883/a-systems-biology-analysis-connects-insulin-receptor-signaling-with-glucose-transporter-translocation-in-rat-adipocytes
#20
Niclas Bergqvist, Elin Nyman, Gunnar Cedersund, Karin G Stenkula
Type 2 diabetes is characterized by insulin resistance, which arises from malfunctions in the intracellular insulin signaling network. Knowledge of the insulin signaling network is fragmented, and because of the complexity of this network, little consensus has emerged for the structure and importance of the different branches of the network. To help overcome this complexity, systems biology mathematical models have been generated for predicting both the activation of the insulin receptor (IR) and the redistribution of glucose transporter 4 (GLUT4) to the plasma membrane...
July 7, 2017: Journal of Biological Chemistry
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