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https://www.readbyqxmd.com/read/28545963/the-carboxy-terminal-region-of-the-tbc1d4-as160-rabgap-mediates-protein-homodimerization
#1
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...
May 22, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28533752/protocatechuic-acid-a-phenolic-from-sansevieria-roxburghiana-leaves-suppresses-diabetic-cardiomyopathy-via-stimulating-glucose-metabolism-ameliorating-oxidative-stress-and-inhibiting-inflammation
#2
Niloy Bhattacharjee, Tarun K Dua, Ritu Khanra, Swarnalata Joardar, Ashis Nandy, Achintya Saha, Vincenzo De Feo, Saikat Dewanjee
Persistent hyperglycemia, impairment of redox status and establishment of inflammatory pathophysiology integrally play important role in the pathogenesis of diabetic cardiomyopathy (DC). Present study examined the therapeutic potential of protocatechuic acid isolated from the Sansevieria roxburghiana rhizomes against DC employing rodent model of type 2 diabetes (T2D). T2D was induced by high fat diet + a low-single dose of streptozotocin (35 mg/kg, i.p.). T2D rats exhibited significantly (p < 0.01) high fasting blood glucose level...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529958/spatiotemporal-regulators-for-insulin-stimulated-glut4-vesicle-exocytosis
#3
REVIEW
Xiaoxu Zhou, Ping Shentu, Yingke Xu
Insulin increases glucose uptake and storage in muscle and adipose cells, which is accomplished through the mobilization of intracellular GLUT4 storage vesicles (GSVs) to the cell surface upon stimulation. Importantly, the dysfunction of insulin-regulated GLUT4 trafficking is strongly linked with peripheral insulin resistance and type 2 diabetes in human. The insulin signaling pathway, key signaling molecules involved, and precise trafficking itinerary of GSVs are largely identified. Understanding the interaction between insulin signaling molecules and key regulatory proteins that are involved in spatiotemporal regulation of GLUT4 vesicle exocytosis is of great importance to explain the pathogenesis of diabetes and may provide new potential therapeutic targets...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28529245/inhibition-of-nf-%C3%AE%C2%BAb-activation-improves-insulin-resistance-of-l6-cells
#4
Fengyang Xie, Jian Zhu, Baolian Hou, Yuan Wang, Fanzhu Meng, Zhixing Ren, Shuping Ren
To explore the role of NF-κB activation in the development of insulin resistance and investigate whether or not that the inhibition of NF-κB activation by PDTC will improve the insulin resistance of L6 cells exposed to H2O2. L6 cells were treated with H2O2, PDTC or both H2O2 and PDTC for 4 hours. The uptake of glucose with stimulation of insulin, the expression of P38-MAPK, p- P38-MAPK, NF-κBp65, p- NF-κBp65, IRS-1, IRS-2, p-IRS-2, PI3K, IκBα, p- IκBα, caspase-8 and GLUT4, the production of ROS, TNF-α, IL-6 and IL-1β as well as the apoptosis rate of L6 cells were determined and compared in L6 treated with H2O2 alone or both H2O2 and PDTC...
May 20, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28528355/increased-retinol-free-rbp4-contributes-to-insulin-resistance-in-gestational-diabetes-mellitus
#5
Yanmin Chen, Ping Lv, Mengkai Du, Zhaoxia Liang, Menglin Zhou, Danqing Chen
PURPOSE: Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. METHODS: Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats...
May 20, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28526321/effects-of-dehp-and-its-metabolite-mehp-on-insulin-signalling-and-proteins-involved-in-glut4-translocation-in-cultured-l6-myotubes
#6
Mangala Priya Viswanathan, Vigneswari Mullainadhan, Mayilvanan Chinnaiyan, Balasubramanian Karundevi
Di-(2-ethylhexyl)phthalate (DEHP) is the plasticizer used in variety of medical and consumer products to impart structural flexibility. DEHP and its primary metabolite mono-(2-ethyl hexyl)phthalate (MEHP) posed a considerable interest because of their contribution to insulin resistance, type-2 diabetes and obesity. Experimental and epidemiological data have shown that DEHP affects blood glucose homeostasis. However, direct effect of DEHP and its metabolite MEHP on insulin signal transduction and glucose transporter 4 (GLUT4) translocation remain obscure...
May 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28513282/zanthoxylum-alkylamides-activate-phosphorylated-ampk-and-ameliorate-glycolipid-metabolism-in-the-streptozotocin-induced-diabetic-rats
#7
Tingyuan Ren, Yuping Zhu, Jianquan Kan
This study aimed to evaluate the effects of Zanthoxylum alkylamides on the glycolipid metabolism of rats with streptozotocin (STZ)-induced diabetes. Diabetic rats were given daily oral treatments of 2, 4, or 8 mg/kg bw alkylamides for 28 days. Alkylamides significantly decreased fasting blood glucose and fructosamine content, as well as relieved organ enlargement caused by diabetes. The serum and liver triglyceride, malondialdehyde, and free fatty-acid contents of rats with STZ-induced diabetes were significantly reduced...
May 17, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28508346/testosterone-insulin-like-effects-an-in-vitro-study-on-the-short-term-metabolic-effects-of-testosterone-in-human-skeletal-muscle-cells
#8
C Antinozzi, F Marampon, C Corinaldesi, E Vicini, P Sgrò, G B Vannelli, A Lenzi, C Crescioli, L Di Luigi
PURPOSE: Testosterone by promoting different metabolic pathways contributes to short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue and the primary site for insulin-stimulated glucose utilization. Despite evidences indicate a close relationship between testosterone and glucose metabolism, the molecular mechanisms responsible for a possible testosterone-mediated insulin-like effects on skeletal muscle are still unknown. METHODS: Here we used undifferentiated proliferating or differentiated human fetal skeletal muscle cells (Hfsmc) to investigate the short-term effects of testosterone on the insulin-mediated biomolecular metabolic machinery...
May 15, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28507343/non-alcoholic-fatty-liver-disease-vascular-inflammation-and-insulin-resistance-are-exacerbated-by-trail-deletion-in-mice
#9
Siân P Cartland, Hanis H Harith, Scott W Genner, Lei Dang, Victoria C Cogger, Melissa Vellozzi, Belinda A Di Bartolo, Shane R Thomas, Leon A Adams, Mary M Kavurma
Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail (-/-) mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28501567/depletion-of-jmjd1c-impairs-adipogenesis-in-murine-3t3-l1-cells
#10
Florian Buerger, Silvana Müller, Nadja Ney, Juliane Weiner, John T Heiker, Sonja Kallendrusch, Peter Kovacs, Dorit Schleinitz, Joachim Thiery, Sonja C Stadler, Ralph Burkhardt
Differentiation of adipocytes is a highly regulated process modulated by multiple transcriptional co-activators and co-repressors. JMJD1C belongs to the family of jumonji C (jmjC) domain-containing histone demethylases and was originally described as a ligand-dependent co-activator of thyroid hormone and androgen receptors. Here, we explored the potential role of Jmjd1c in white adipocyte differentiation. To investigate the relevance of Jmjd1c in adipogenesis, murine 3T3-L1 preadipocyte cells with transient knock-down of Jmjd1c (3T3_Jmjd1c) were generated...
May 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28500736/high-density-lipoprotein-hdl-reverses-palmitic-acid-induced-energy-metabolism-imbalance-by-switching-cd36-and-glut4-signaling-pathways-in-cardiomyocyte
#11
Su-Ying Wen, Bharath Kumar Velmurugan, Cecilia Hsuan Day, Chia-Yao Shen, Li-Chin Chun, Yi-Chieh Tsai, Yueh-Min Lin, Ray-Jade Chen, Chia-Hua Kuo, Chih-Yang Huang
In our previous study palmitic acid (PA) induced lipotoxicity and switches energy metabolism from CD36 to GLUT4 in H9c2 cells. Low level of high density lipoprotein (HDL) is an independent risk factor for cardiac hypertrophy. Therefore we in the present study investigated whether HDL can reverse PA induced lipotoxicity in H9c2 cardiomyoblast cells. In this study, we treated H9c2 cells with PA to create a hyperlipidemia model in vitro and analyzed for CD36 and GLUT4 metabolic pathway proteins. CD36 metabolic pathway proteins (phospho-AMPK, SIRT1, PGC1α, PPARα, CPT1β and CD36) were decreased by high PA (150 and 200 µg/µL) concentration...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28495883/a-systems-biology-analysis-connects-insulin-receptor-signaling-with-glucose-transporter-translocation-in-rat-adipocytes
#12
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/28490443/peripheral-insulin-resistance-in-ilk-depleted-mice-by-reduction-of-glut4-expression
#13
Marco Hatem-Vaquero, Mercedes Griera, Andrea Garcia-Jerez, Alicia Luengo, Julia Alvarez-Hernandez, Jose Antonio Rubio-Garcia, Laura Calleros, Diego Rodriguez-Puyol, Manuel Rodriguez-Puyol, Sergio de Frutos
The development of insulin resistance is characterized by the impairment of glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix changes are induced when the metabolic dysregulation is sustained. The present work was devoted to analyze the possible link between the extracellular-to-intracellular mediator integrin linked kinase (ILK) and the peripheral tissue modification that leads to glucose homeostasis impairment. Mice with general depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited increased glycaemia and insulinemia concurrently with a reduction of the expression and membranes presence of GLUT4 in the insulin-sensitive peripheral tissues compared with their wildtype littermates (WT)...
May 10, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28485800/gdf11-does-not-improve-the-palmitate-induced-insulin-resistance-in-c2c12
#14
Y-Y Jing, D Li, F Wu, L-L Gong, R Li
OBJECTIVE: GDF11 (Growth Differentiation factor 11) has been reported to rejuvenate skeletal muscle, heart and brain in aged mice, and the aged skeletal muscle is closely related to insulin resistance. We wondered whether GDF11 has an effect on skeletal muscle insulin resistance. MATERIALS AND METHODS: High fat diet induced obese mice with insulin resistance were established in vivo. Palmitate-induced insulin resistance in C2C12 myotubes was established in vitro...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28483437/4-phenyl-butyric-acid-increases-particulate-hexokinase-activity-and-protects-against-ros-injury-in-l6-myotubes
#15
Michele Hinerasky da Silva, Flavia Letícia Martins Peçanha, Aline Machado de Oliveira, Wagner Seixas da-Silva
Hexokinase (HK) is the first enzyme in the glycolytic pathway and is responsible for glucose phosphorylation and fixation into the cell. HK (HK-II) is expressed in skeletal muscle and can be found in the cytosol or bound mitochondria, where it can protect cells against insults such as oxidative stress. 4-Phenyl butyric acid (4-PBA) is a chemical chaperone that inhibits endoplasmic reticulum stress and contributes to the restoring of glucose homeostasis. AIMS: Here, we decided to investigate whether HK activity and its interaction with mitochondria could be a target of 4-PBA action...
May 5, 2017: Life Sciences
https://www.readbyqxmd.com/read/28482944/increased-birth-weight-is-associated-with-altered-gene-expression-in-neonatal-foreskin
#16
L J Reynolds, R I Pollack, R J Charnigo, C S Rashid, A J Stromberg, S Shen, J M O'Brien, K J Pearson
Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v...
May 9, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28476619/trb3-gene-silencing-activates-ampk-in-adipose-tissue-with-beneficial-metabolic-effects-in-obese-and-diabetic-rats
#17
Xiaoyan Sun, Ming Song, Hui Wang, Huimin Zhou, Feng Wang, Ya Li, Yun Zhang, Wei Zhang, Ming Zhong, Yun Ti
Our previous study had suggested Tribbles homolog 3 (TRB3) might be involved in metabolic syndrome via adipose tissue. Given prior studies, we sought to determine whether TRB3 plays a major role in adipocytes and adipose tissue with beneficial metabolic effects in obese and diabetic rats. Fully differentiated 3T3-L1 adipocytes were incubated to induce insulin resistant adipocytes. Forty male Sprague-Dawley rats were all fed high-fat (HF) diet. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin (STZ)...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28474889/promotion-of-glucose-uptake-in-c2c12-myotubes-by-cereal-flavone-tricin-and-its-underlying-molecular-mechanism
#18
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/28464351/mtorc2-regulates-muscle-glucose-uptake-during-exercise-in-mice
#19
Maximilian Kleinert, Benjamin L Parker, Andreas M Fritzen, Jonas R Knudsen, Thomas E Jensen, Rasmus Kjøbsted, Lykke Sylow, Markus Ruegg, David E James, Erik A Richter
Exercise increases glucose uptake into insulin-resistant muscle. Thus, elucidating the exercise signalling network in muscle may uncover new therapeutic targets. mTORC2, a regulator of insulin-controlled glucose uptake, has been reported to interact with Rac1, which plays a role in exercise-induced glucose uptake in muscle. Therefore, we tested the hypothesis that mTORC2 activity is necessary for muscle glucose uptake during treadmill exercise. We used mice that specifically lack mTORC2 signalling in muscle, by deletion of the obligatory mTORC2 component, Rictor (Ric mKO)...
May 2, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28462458/crossreactivity-of-an-antiserum-directed-to-the-gram-negative-bacterium-neisseria-gonorrhoeae-with-the-snare-complex-protein-snap23-correlates-to-impaired-exocytosis-in-sh-sy5y-cells
#20
A Almamy, C Schwerk, H Schroten, H Ishikawa, A R Asif, B Reuss
Early maternal infections with Neisseria gonorrhoeae (NG) correlate to an increased lifetime schizophrenia risk for the offspring, which might be due to an immune-mediated mechanism. Here, we investigated the interactions of polyclonal antisera to NG (α-NG) with a first trimester prenatal brain multiprotein array, revealing among others the SNARE-complex protein Snap23 as a target antigen for α-NG. This interaction was confirmed by Western blot analysis with a recombinant Snap23 protein, whereas the closely related Snap25 failed to interact with α-NG...
May 1, 2017: Journal of Molecular Neuroscience: MN
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