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https://www.readbyqxmd.com/read/28522731/effect-of-metformin-on-bioactive-lipid-metabolism-in-insulin-resistant-muscle
#1
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
#2
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...
May 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28487439/roux-en-y-gastric-bypass-surgery-enhances-contraction-mediated-glucose-metabolism-in-primary-human-myotubes
#3
J Matthew Hinkley, Kai Zou, Sanghee Park, Kristen Turner, Donghai Zheng, Joseph A Houmard
Contractile activity (e.g. exercise) evokes numerous metabolic adaptations in human skeletal muscle including enhanced insulin action and substrate oxidation. However, there is inter-subject variation in the physiological responses to exercise, which may be linked with factors such as the degree of obesity. Roux-en-Y gastric bypass (RYGB) surgery reduces body mass in severely obese (BMI > 40 kg/m(2)) individuals; however, it is uncertain whether RYGB can potentiate responses to contractile activity in this potentially exercise-resistant population...
May 9, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28474889/promotion-of-glucose-uptake-in-c2c12-myotubes-by-cereal-flavone-tricin-and-its-underlying-molecular-mechanism
#4
Sohyun Kim, Gwang-Woong Go, Jee-Young Imm
The effect of tricin, a methylated flavone widely distributed in cereals, on glucose uptake and the underlying molecular mechanism was investigated using C2C12 myotubes. Tricin significantly increased glucose uptake in C2C12 myotubes, regardless of the absence (1.4-fold at 20 μM) or presence (1.6-fold at 20 μM) of insulin. The GLUT4 expression on the plasma membrane was increased 1.6-fold after tricin treatment (20 μM) in the absence of insulin. Tricin treatment significantly activated the insulin-dependent cell signaling pathway, including the activation of insulin receptor substrate-1 (IRS1), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and AKT substrate of 160 kDa (AS160)...
May 5, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28431322/xanthohumol-and-8-prenylnaringenin-ameliorate-diabetic-related-metabolic-dysfunctions-in-mice
#5
Raquel Costa, Ilda Rodrigues, Luísa Guardão, Sílvia Rocha-Rodrigues, Carolina Silva, José Magalhães, Manuel Ferreira-de-Almeida, Rita Negrão, Raquel Soares
Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by metabolic disturbances in specific tissues. The present work aimed to analyze the effects of xanthohumol (XN) and 8-prenylnaringenin (8PN), two beer-derived polyphenols, in liver and skeletal muscle lipid and glycolytic metabolism in T2DM mice model. Thirty C57Bl/6 mice were randomly divided into five groups: standard diet (control), high-fat diet (DM), high-fat diet plus ethanol (DM-Ethanol), high-fat diet plus 10 mg/L XN (DM-XN) and high-fat diet plus 10 mg/L 8PN (DM-8PN) during 20 weeks...
April 6, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28365702/akt2-dependent-beneficial-effect-of-galanin-on-insulin-induced-glucose-uptake-in-adipocytes-of-diabetic-rats
#6
Zhenwen Zhang, Penghua Fang, Lili Guo, Biao He, Mingyi Shi, Yan Zhu, Ping Bo
BACKGROUND/AIMS: Glucose uptake occurs via the activation of an insulin-signaling cascade, resulting in the translocation of glucose transporter 4 (GLUT4) to the plasma membrane of adipocytes and myocytes. Recent research found that galanin could boost insulin-induced glucose uptake. This study aimed to explore whether activation of Akt2 mediates the beneficial effects of galanin on insulin-induced glucose uptake in the adipocytes of diabetic rats. METHOD: In this experiment, insulin, galanin and MK-2206, an Akt inhibitor, were injected individually or in combination into diabetic rats once a day for ten days...
March 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28359800/baicalin-against-obesity-and-insulin-resistance-through-activation-of-akt-as160-glut4-pathway
#7
Penghua Fang, Mei Yu, Lei Zhang, Dan Wan, Mingyi Shi, Yan Zhu, Ping Bo, Zhenwen Zhang
Obesity may cause several metabolic complications, including insulin resistance and type 2 diabetes mellitus. Despite great advances in medicine, people still keep exploring novel and effective drugs for treatment of obesity and insulin resistance. The aim of this study was to survey if baicalin might ameliorate obesity-induced insulin resistance and to explore its signal mechanisms in skeletal muscles of mice. Diet-induced obese (DIO) mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 days, and C2C12 myotubes were treated with 100, 200, 400 μM baicalin for 12 h in this study...
March 27, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28252104/altered-gene-expression-and-repressed-markers-of-autophagy-in-skeletal-muscle-of-insulin-resistant-patients-with-type-2-diabetes
#8
Andreas Buch Møller, Ulla Kampmann, Jakob Hedegaard, Kasper Thorsen, Iver Nordentoft, Mikkel Holm Vendelbo, Niels Møller, Niels Jessen
This case-control study was designed to investigate the gene expression profile in skeletal muscle from severely insulin resistant patients with long-standing type 2 diabetes (T2D), and to determine associated signaling pathways. Gene expression profiles were examined by whole transcriptome, strand-specific RNA-sequencing and associated signaling was determined by western blot. We identified 117 differentially expressed gene transcripts. Ingenuity Pathway Analysis related these differences to abnormal muscle morphology and mitochondrial dysfunction...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28218490/comparative-effects-of-energy-restriction-and-resveratrol-intake-on-glycemic-control-improvement
#9
I Milton-Laskibar, L Aguirre, M T Macarulla, U Etxeberria, F I Milagro, J A Martínez, J Contreras, M P Portillo
Resveratrol (RSV) has been proposed as an energy restriction mimetic. This study aimed to compare the effects of RSV and energy restriction on insulin resistance induced by an obesogenic diet. Any additive effect of both treatments was also analyzed. Rats were fed a high-fat high-sucrose diet for 6 weeks. They were then distributed in four experimental groups which were either fed a standard control diet (C), or treated with RSV (30 mg/kg/d), or submitted to energy restriction (R, 15%), or treated with RSV and submitted to energy restriction (RR)...
February 20, 2017: BioFactors
https://www.readbyqxmd.com/read/28214558/small-heterodimer-partner-shp-contributes-to-insulin-resistance-in-cardiomyocytes
#10
Ricardo Rodríguez-Calvo, Dipanjan Chanda, Yvonne Oligschlaeger, Marie Miglianico, Will A Coumans, Emma Barroso, Marta Tajes, Joost Jfp Luiken, Jan Fc Glatz, Manuel Vázquez-Carrera, Dietbert Neumann
Small heterodimer partner (SHP) is an atypical nuclear receptor expressed in heart that has been shown to inhibit the hypertrophic response. Here, we assessed the role of SHP in cardiac metabolism and inflammation. Mice fed a high-fat diet (HFD) displayed glucose intolerance accompanied by increased cardiac mRNA levels of Shp. In HL-1 cardiomyocytes, SHP overexpression inhibited both basal and insulin-stimulated glucose uptake and impaired the insulin signalling pathway (evidenced by reduced AKT and AS160 phosphorylation), similar to insulin resistant cells generated by high palmitate/high insulin treatment (HP/HI; 500μM/100nM)...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28177704/the-rab-gtpase-activating-protein-tbc1d1-is-critical-for-maintaining-normal-glucose-homeostasis-and-%C3%AE-cell-mass
#11
Sabina Paglialunga, Genevieve Simnett, Holly Robson, Monica Hoang, Renjitha Pillai, Alicia M Arkell, Jeremy A Simpson, Arend Bonen, Mark Huising, Jamie W Joseph, Graham P Holloway
TBC1D1, a Rab-GTPase activating protein, is a paralogue of AS160, and has been implicated in the canonical insulin-signaling cascade in peripheral tissues. More recently, TBC1D1 was identified in rat and human pancreatic islets, however the islet function of TBC1D1 remains not fully understood. We examined the role of TBC1D1 in glucose homeostasis and insulin secretion utilizing a rat knockout (KO) model. Chow-fed TBC1D1 KO rats had improved insulin action but impaired glucose-tolerance test (GTT) and a lower insulin response during an ipGTT compared to WT rats...
January 31, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28096436/angiotensin-ii-induces-differential-insulin-action-in-rat-skeletal-muscle
#12
Juthamard Surapongchai, Mujalin Prasannarong, Tepmanas Bupha-Intr, Vitoon Saengsirisuwan
Angiotensin II (ANGII) is reportedly involved in the development of skeletal muscle insulin resistance. The present investigation evaluated the effects of two ANGII doses on the phenotypic characteristics of insulin resistance syndrome and insulin action and signaling in rat skeletal muscle. Male Sprague-Dawley rats were infused with either saline (SHAM) or ANGII at a commonly used pressor dose (100 ng/kg/min; ANGII-100) or a higher pressor dose (500 ng/kg/min; ANGII-500) via osmotic minipumps for 14 days...
January 17, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#13
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
April 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28008588/losartan-improves-palmitate-induced-insulin-resistance-in-3t3-l1-adipocytes-through-upregulation-of-src-phosphorylation
#14
X Tian, M Ye, Y Cao, C Wang
Angiotensin II type 1 receptor blocker losartan has shown strongly anti-insulin resistance properties in vivo and in vitro; however, the underlying mechanisms are poorly understood. In this study, we demonstrate that losartan administration increased phosphorylation of Akt and its downstream Akt substrate of 160 kDa (AS160), enhanced plasma membrane translocation of glucose transporter type 4 (GLUT4), and increased glucose uptake, along with increased Src phosphorylation as well as reduced expression of docking protein 1(DOK1) in palmitate-treated 3T3-L1 adipocytes...
February 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/27966646/insulin-induced-effects-on-the-subcellular-localization-of-akt1-akt2-and-as160-in-rat-skeletal-muscle
#15
Xiaohua Zheng, Gregory D Cartee
AKT1 and AKT2, the AKT isoforms that are highly expressed in skeletal muscle, have distinct and overlapping functions, with AKT2 more important for insulin-stimulated glucose metabolism. In adipocytes, AKT2 versus AKT1 has greater susceptibility for insulin-mediated redistribution from cytosolic to membrane localization, and insulin also causes subcellular redistribution of AKT Substrate of 160 kDa (AS160), an AKT2 substrate and crucial mediator of insulin-stimulated glucose transport. Although skeletal muscle is the major tissue for insulin-mediated glucose disposal, little is known about AKT1, AKT2 or AS160 subcellular localization in skeletal muscle...
December 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903431/differential-regulation-of-baicalin-and-scutellarin-on-ampk-and-akt-in-promoting-adipose-cell-glucose-disposal
#16
Le-Le Yang, Na Xiao, Jinfeng Liu, Kang Liu, Baolin Liu, Ping Li, Lian-Wen Qi
Baicalin and scutellarin, two flavonoid glucuronic acids isolated from Scutellaria baicalensis, exhibit beneficial effects on glucose homeostasis. Baicalin and scutellarin are similar in structure except scutellarin has an additional hydroxyl at composition C-4'. In this work, we observed that baicalin and scutellarin promoted glucose disposal in mice and in adipocytes. Baicalin selectively increased phosphorylation of AMP-activated kinase (AMPK), while scutellarin selectively enhanced Akt phosphorylation. Both of them increased AS160 phosphorylation and glucose uptake in basal condition...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27834291/sex-differences-in-the-metabolic-dysfunction-and-insulin-resistance-of-skeletal-muscle-glucose-transport-following-high-fructose-ingestion
#17
Yupaporn Rattanavichit, Natsasi Chukijrungroat, Vitoon Saengsirisuwan
The role of high fructose ingestion (HFI) in the development of conditions mimicking human metabolic syndrome has mostly been demonstrated in male animals; however, the extent of HFI-induced metabolic alterations in females remains unclear. The present study investigated whether HFI-induced metabolic perturbations differ between sexes and whether HFI aggravates the metabolic disturbances under ovarian hormone deprivation. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were given either water or liquid fructose (10% wt/vol) for 6 wk...
December 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27714805/challenging-of-as160-tbc1d4-alters-intracellular-lipid-milieu-in-l6-myotubes-incubated-with-palmitate
#18
Agnieszka Mikłosz, Bartłomiej Łukaszuk, Małgorzata Żendzian-Piotrowska, Justyna Brańska-Januszewska, Halina Ostrowska, Adrian Chabowski
The Akt substrate of 160 kDa (AS160) is a key regulator of GLUT4 translocation from intracellular depots to the plasma membrane in myocytes. Likely, AS160 also controls LCFAs transport, which requires relocation of fatty acid transporters. The aim of the present study was to determine the impact of AS160 knockdown on lipid milieu in L6 myotubes incubated with palmitate (PA). Therefore, we compared two different settings, namely: 1) AS160 knockdown prior to palmitate incubation (pre-PA-silencing, AS160(-) /PA); 2) palmitate incubation with subsequent AS160 knockdown (post-PA-silencing, PA/AS160(-) )...
September 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27695421/acute-high-intensity-interval-exercise-induced-redox-signaling-is-associated-with-enhanced-insulin-sensitivity-in-obese-middle-aged-men
#19
Lewan Parker, Nigel K Stepto, Christopher S Shaw, Fabio R Serpiello, Mitchell Anderson, David L Hare, Itamar Levinger
Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27554475/the-inactivation-of-rabgap-function-of-as160-promotes-lysosomal-degradation-of-glut4-and-causes-postprandial-hyperglycemia-and-hyperinsulinemia
#20
Bingxian Xie, Qiaoli Chen, Liang Chen, Yang Sheng, Hong Yu Wang, Shuai Chen
The AS160 (Akt substrate of 160 kDa) is a Rab-GTPase activating protein (RabGAP) with several other functional domains, and its deficiency in mice or human patients lowers GLUT4 protein levels and causes severe insulin resistance. How its deficiency causes diminished GLUT4 proteins remains unknown. We found that the deletion of AS160 decreased GLUT4 levels in a cell/tissue-autonomous manner. Consequently, skeletal muscle-specific deletion of AS160 caused postprandial hyperglycemia and hyperinsulinemia. The pathogenic effects of AS160 deletion are mainly, if not exclusively, due to the loss of its RabGAP function since the RabGAP-inactive AS160(R917K) mutant mice phenocopied the AS160 knockout mice...
November 2016: Diabetes
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