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https://www.readbyqxmd.com/read/29784647/regulation-of-rabgaps-involved-in-insulin-action
#1
REVIEW
Samaneh Mafakheri, Alexandra Chadt, Hadi Al-Hasani
Rab (Ras-related proteins in brain) GTPases are key proteins responsible for a multiplicity of cellular trafficking processes. Belonging to the family of monomeric GTPases, they are regulated by cycling between their active GTP-bound and inactive GDP-bound conformations. Despite possessing a slow intrinsic GTP hydrolysis activity, Rab proteins rely on RabGAPs (Rab GTPase-activating proteins) that catalyze GTP hydrolysis and consequently inactivate the respective Rab GTPases. Two related RabGAPs, TBC1D1 and TBC1D4 (=AS160) have been described to be associated with obesity-related traits and type 2 diabetes in both mice and humans...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29720080/genome-wide-scan-reveals-population-stratification-and-footprints-of-recent-selection-in-nelore-cattle
#2
Diercles F Cardoso, Lucia Galvão de Albuquerque, Christian Reimer, Saber Qanbari, Malena Erbe, André V do Nascimento, Guilherme C Venturini, Daiane C Becker Scalez, Fernando Baldi, Gregório M Ferreira de Camargo, Maria E Zerlotti Mercadante, Joslaine N do Santos Gonçalves Cyrillo, Henner Simianer, Humberto Tonhati
BACKGROUND: This study aimed at (1) assessing the genomic stratification of experimental lines of Nelore cattle that have experienced different selection regimes for growth traits, and (2) identifying genomic regions that have undergone recent selection. We used a sample of 763 animals genotyped with the Illumina BovineHD BeadChip, among which 674 animals originated from two lines that are maintained under directional selection for increased yearling body weight and 89 animals from a control line that is maintained under stabilizing selection...
May 2, 2018: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/29574752/whole-body-arhgap21-reduction-improves-glucose-homeostasis-in-high-fat-diet-obese-mice
#3
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
https://www.readbyqxmd.com/read/29481597/deletion-of-the-rabgap-tbc1d1-leads-to-enhanced-insulin-secretion-and-fatty-acid-oxidation-in-islets-from-male-mice
#4
Torben Stermann, Franziska Menzel, Carmen Weidlich, Kay Jeruschke, Jürgen Weiss, Delsi Altenhofen, Tim Benninghoff, Anna Pujol, Fatima Bosch, Ingo Rustenbeck, D Margriet Ouwens, G Hege Thoresen, Christian de Wendt, Sandra Lebek, Tanja Schallschmidt, Martin Kragl, Eckhard Lammert, Alexandra Chadt, Hadi Al-Hasani
The Rab guanosine triphosphatase-activating protein (RabGAP) TBC1D1 has been shown to be a key regulator of glucose and lipid metabolism in skeletal muscle. Its function in pancreatic islets, however, is not yet fully understood. Here, we aimed to clarify the specific impact of TBC1D1 on insulin secretion and substrate use in pancreatic islets. We analyzed the dynamics of glucose-stimulated insulin secretion (GSIS) and lipid metabolism in isolated islets from Tbc1d1-deficient (D1KO) mice. To further investigate the underlying cellular mechanisms, we conducted pharmacological studies in these islets...
April 1, 2018: Endocrinology
https://www.readbyqxmd.com/read/29247648/pkc-and-rab13-mediate-ca-2-signal-regulated-glut4-traffic
#5
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...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29216901/genomic-variants-in-the-fto-gene-are-associated-with-sporadic-amyotrophic-lateral-sclerosis-in-greek-patients
#6
Konstantinos Mitropoulos, Eleni Merkouri Papadima, Georgia Xiromerisiou, Angeliki Balasopoulou, Kyriaki Charalampidou, Vasiliki Galani, Krystallia-Vassiliki Zafeiri, Efthymios Dardiotis, Styliani Ralli, Georgia Deretzi, Anne John, Kyriaki Kydonopoulou, Elpida Papadopoulou, Alba di Pardo, Fulya Akcimen, Annalisa Loizedda, Valerija Dobričić, Ivana Novaković, Vladimir S Kostić, Clint Mizzi, Brock A Peters, Nazli Basak, Sandro Orrù, Evangelos Kiskinis, David N Cooper, Spyridon Gerou, Radoje Drmanac, Marina Bartsakoulia, Evangelia-Eirini Tsermpini, Georgios M Hadjigeorgiou, Bassam R Ali, Theodora Katsila, George P Patrinos
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS). RESULTS: Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTO and TBC1D1 gene variants and sALS...
December 8, 2017: Human Genomics
https://www.readbyqxmd.com/read/29089333/electrical-pulse-stimulation-induces-glut4-glucose-transporter-translocation-in-c2c12-myotubes-that-depends-on-rab8a-rab13-and-rab14
#7
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-GLUT4 HA) that contract in response to electrical pulse stimulation (EPS) and investigated molecular mechanisms regulating GLUT4 HA. EPS (60min, 20V, 1Hz, 24ms pulses at 976ms intervals) elicited a gain in surface GLUT4 HA (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/28890999/a-genome-wide-association-study-identifies-genomic-loci-associated-with-backfat-thickness-carcass-weight-and-body-weight-in-two-commercial-pig-populations
#8
Yuanmei Guo, Hengqing Qiu, Shijun Xiao, Zhenfang Wu, Ming Yang, Jie Yang, Jun Ren, Lusheng Huang
Growth and fatness traits are economically important in the pig industry. To dissect the genetic architecture of these traits in commercial pigs, we conducted a genome-wide association study (GWAS) for carcass weight, backfat thickness, and body weight in two commercial populations: Duroc × (Landrace × Yorkshire) (DLY) and Duroc populations. To enhance the detection power, three GWAS approaches including single-trait GWAS, multi-trait GWAS and meta-analysis were used in this study. A total of 13 suggestive loci were identified on nine chromosomes...
November 2017: Journal of Applied Genetics
https://www.readbyqxmd.com/read/28882901/chronic-intermittent-hypoxia-impairs-insulin-sensitivity-but-improves-whole-body-glucose-tolerance-by-activating-skeletal-muscle-ampk
#9
Amandine Thomas, Elise Belaidi, Sophie Moulin, Sandrine Horman, Gerard C van der Zon, Benoit Viollet, Patrick Levy, Luc Bertrand, Jean-Louis Pepin, Diane Godin-Ribuot, Bruno Guigas
Obstructive sleep apnea syndrome is a highly prevalent disease resulting in transient respiratory arrest and chronic intermittent hypoxia (cIH). cIH is associated with insulin resistance and impaired metabolic homeostasis in rodents and humans, but the exact underlying mechanisms remain unclear. In the current study, we investigated the effects of 2 weeks of cIH (1-min cycle, fraction of inspired oxygen 21-5%, 8 h/day) on whole-body insulin sensitivity and glucose tolerance in lean mice. Although food intake and body weight were reduced compared with normoxia, cIH induced systemic insulin resistance in a hypoxia-inducible factor 1-independent manner and impaired insulin signaling in liver, white adipose tissue, and skeletal muscle...
December 2017: Diabetes
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
#10
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/28602209/update-on-glut4-vesicle-traffic-a-cornerstone-of-insulin-action
#11
REVIEW
Javier R Jaldin-Fincati, Martin Pavarotti, Scott Frendo-Cumbo, Philip J Bilan, Amira Klip
Glucose transport is rate limiting for dietary glucose utilization by muscle and fat. The glucose transporter GLUT4 is dynamically sorted and retained intracellularly and redistributes to the plasma membrane (PM) by insulin-regulated vesicular traffic, or 'GLUT4 translocation'. Here we emphasize recent findings in GLUT4 translocation research. The application of total internal reflection fluorescence microscopy (TIRFM) has increased our understanding of insulin-regulated events beneath the PM, such as vesicle tethering and membrane fusion...
August 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28177704/the-rab-gtpase-activating-protein-tbc1d1-is-critical-for-maintaining-normal-glucose-homeostasis-and-%C3%AE-cell-mass
#12
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
Tre-2/USP6, BUB2, cdc16 domain family, member 1 (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 tests (GTT) and a lower insulin response during an intraperitoneal GTT compared with wild-type (WT) rats...
January 31, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28168758/crystal-structure-of-tbc1d15-gtpase-activating-protein-gap-domain-and-its-activity-on-rab-gtpases
#13
Yan-Na Chen, Xin Gu, X Edward Zhou, Weidong Wang, Dandan Cheng, Yinghua Ge, Fei Ye, H Eric Xu, Zhengbing Lv
TBC1D15 belongs to the TBC (Tre-2/Bub2/Cdc16) domain family and functions as a GTPase-activating protein (GAP) for Rab GTPases. So far, the structure of TBC1D15 or the TBC1D15·Rab complex has not been determined, thus, its catalytic mechanism on Rab GTPases is still unclear. In this study, we solved the crystal structures of the Shark and Sus TBC1D15 GAP domains, to 2.8 Å and 2.5 Å resolution, respectively. Shark-TBC1D15 and Sus-TBC1D15 belong to the same subfamily of TBC domain-containing proteins, and their GAP-domain structures are highly similar...
April 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28030618/whole-genome-resequencing-of-holstein-bulls-for-indel-discovery-and-identification-of-genes-associated-with-milk-composition-traits-in-dairy-cattle
#14
Jianping Jiang, Yahui Gao, Yali Hou, Wenhui Li, Shengli Zhang, Qin Zhang, Dongxiao Sun
The use of whole-genome resequencing to obtain more information on genetic variation could produce a range of benefits for the dairy cattle industry, especially with regard to increasing milk production and improving milk composition. In this study, we sequenced the genomes of eight Holstein bulls from four half- or full-sib families, with high and low estimated breeding values (EBVs) of milk protein percentage and fat percentage at an average effective depth of 10×, using Illumina sequencing. Over 0.9 million nonredundant short insertions and deletions (indels) [1-49 base pairs (bp)] were obtained...
2016: PloS One
https://www.readbyqxmd.com/read/27826658/a-tbc1d1-ser231ala-knockin-mutation-partially-impairs-aicar-but-not-exercise-induced-muscle-glucose-uptake-in-mice
#15
Qiaoli Chen, Bingxian Xie, Sangsang Zhu, Ping Rong, Yang Sheng, Serge Ducommun, Liang Chen, Chao Quan, Min Li, Kei Sakamoto, Carol MacKintosh, Shuai Chen, Hong Yu Wang
AIMS/HYPOTHESIS: TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) is a Rab GTPase-activating protein (RabGAP) that has been implicated in regulating GLUT4 trafficking. TBC1D1 can be phosphorylated by the AMP-activated protein kinase (AMPK) on Ser231 , which consequently interacts with 14-3-3 proteins. Given the key role for AMPK in regulating insulin-independent muscle glucose uptake, we hypothesised that TBC1D1-Ser231 phosphorylation and/or 14-3-3 binding may mediate AMPK-governed glucose homeostasis...
February 2017: Diabetologia
https://www.readbyqxmd.com/read/27550988/acute-resistance-exercise-induced-igf1-expression-and-subsequent-glut4-translocation
#16
Kohei Kido, Satoru Ato, Takumi Yokokawa, Yuhei Makanae, Koji Sato, Satoshi Fujita
Acute aerobic exercise (AE) is a major physiological stimulus for skeletal muscle glucose uptake through activation of 5' AMP-activated protein kinase (AMPK). However, the regulation of glucose uptake by acute resistance exercise (RE) remains unclear. To investigate the intracellular regulation of glucose uptake after acute RE versus acute AE, male Sprague-Dawley rats were divided into three groups: RE, AE, or nonexercise control. After fasting for 12 h overnight, the right gastrocnemius muscle in the RE group was exercised at maximum isometric contraction via percutaneous electrical stimulation (3 × 10 sec, 5 sets)...
August 2016: Physiological Reports
https://www.readbyqxmd.com/read/27500534/correction-%C3%AE-msh-stimulates-glucose-uptake-in-mouse-muscle-and-phosphorylates-rab-gtpase-activating-protein-tbc1d1-independently-of-ampk
#17
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0157027.].
2016: PloS One
https://www.readbyqxmd.com/read/27467141/%C3%AE-msh-stimulates-glucose-uptake-in-mouse-muscle-and-phosphorylates-rab-gtpase-activating-protein-tbc1d1-independently-of-ampk
#18
Cathrine Laustrup Møller, Rasmus Kjøbsted, Pablo J Enriori, Thomas Elbenhardt Jensen, Cecilia Garcia-Rudaz, Sara A Litwak, Kirsten Raun, Jørgen Wojtaszewski, Birgitte Schjellerup Wulff, Michael A Cowley
The melanocortin system includes five G-protein coupled receptors (family A) defined as MC1R-MC5R, which are stimulated by endogenous agonists derived from proopiomelanocortin (POMC). The melanocortin system has been intensely studied for its central actions in body weight and energy expenditure regulation, which are mainly mediated by MC4R. The pituitary gland is the source of various POMC-derived hormones released to the circulation, which raises the possibility that there may be actions of the melanocortins on peripheral energy homeostasis...
2016: PloS One
https://www.readbyqxmd.com/read/27307439/disruption-of-the-ampk-tbc1d1-nexus-increases-lipogenic-gene-expression-and-causes-obesity-in-mice-via-promoting-igf1-secretion
#19
Liang Chen, Qiaoli Chen, Bingxian Xie, Chao Quan, Yang Sheng, Sangsang Zhu, Ping Rong, Shuilian Zhou, Kei Sakamoto, Carol MacKintosh, Hong Yu Wang, Shuai Chen
Tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC domain is the GTPase activating protein domain) (TBC1D1) is a Rab GTPase activating protein that is phosphorylated on Ser(231) by the AMP-activated protein kinase (AMPK) in response to intracellular energy stress. However, the in vivo role and importance of this phosphorylation event remains unknown. To address this question, we generated a mouse model harboring a TBC1D1(Ser231Ala) knockin (KI) mutation and found that the KI mice developed obesity on a normal chow diet...
June 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27089993/tbc1d1-deletion-suppresses-obesity-in-leptin-deficient-mice
#20
J Dokas, A Chadt, H-G Joost, H Al-Hasani
BACKGROUND: Variants in the gene TBC1D1 have been previously associated with obesity-related traits in several species, including humans, mice, rabbits and chicken. While in humans variants in TBC1D1 were linked to obesity, disruption of the Tbc1d1 gene reduced body weight in mice. TBC1D1 has been identified as a regulator of insulin-dependent glucose transport in skeletal muscle, however, its role in energy homeostasis in the obese state remains unclear. The impact of TBC1D1 deficiency on energy homeostasis, glucose and lipid metabolism in an established mouse model of obesity was examined...
August 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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