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Muscle insulin resistance

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https://www.readbyqxmd.com/read/29684031/computationally-identified-novel-agonists-for-gprc6a
#1
Min Pi, Karan Kapoor, Ruisong Ye, Dong-Jin Hwang, Duane D Miller, Jeremy C Smith, Jerome Baudry, L Darryl Quarles
New insights into G protein coupled receptor regulation of glucose metabolism by β-cells, skeletal muscle and liver hepatocytes identify GPRC6A as a potential therapeutic target for treating type 2 diabetes mellitus (T2D). Activating GPRC6A with a small molecule drug represents a potential paradigm-shifting opportunity to make significant strides in regulating glucose homeostasis by simultaneously correcting multiple metabolic derangements that underlie T2D, including abnormalities in β-cell proliferation and insulin secretion and peripheral insulin resistance...
2018: PloS One
https://www.readbyqxmd.com/read/29679925/tocotrienol-rich-fraction-supplementation-reduces-hyperglycemia-induced-skeletal-muscle-damage-through-regulation-of-insulin-signaling-and-oxidative-stress-in-type-2-diabetic-mice
#2
Heaji Lee, Yunsook Lim
Chronic hyperglycemia induces impairment of muscle growth and development of diabetes mellitus (DM). Since skeletal muscle is the major site for disposal of ingested glucose, impaired glucose metabolism causes imbalance between protein synthesis and degradation which adversely affects physical mobility. In this study, we investigated the effect of tocotrienol-rich fraction (TRF) supplementation on skeletal muscle damage in diabetic mice. Diabetes was induced by a high-fat diet with streptozotocin (STZ) injection (100 mg/kg) in male C57BL/6J mice...
March 21, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29679905/qing-brick-tea-qbt-aqueous-extract-protects-monosodium-glutamate-induced-obese-mice-against-metabolic-syndrome-and-involves-up-regulation-transcription-factor-nuclear-factor-erythroid-2-related-factor-2-nrf2-antioxidant-pathway
#3
Wenqi Gao, Changyi Xiao, Jun Hu, Biaoxin Chen, Chunyan Wang, Bangping Cui, Pengyi Deng, Jian Yang, Zhifang Deng
BACKGROUND: Qing brick tea (QBT), traditional and popular beverage for Chinese people, is an important post-fermentation dark tea. Our present study was performed to investigate the ameliorative effects of QBT aqueous extract on metabolic syndrome (Mets) in monosodium glutamate-induced obese mice and the potential mechanisms. METHOD: Monosodium glutamate-induced obese mice were used to evaluate the anti-Mets effects of QBT. Content levels of malonaldehyde (MDA), reactive oxygen species (ROS) and protein carbonylation, antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR) in the skeletal muscle were assessed by commercial kits, respectively...
April 18, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29679542/treatments-for-diabetes-mellitus-type-ii-new-perspectives-regarding-the-possible-role-of-calcium-and-camp-interaction
#4
REVIEW
Diego Soares Carvalho, Alexandre Aparecido de Almeida, Aurélio Ferreira Borges, Diego Vannucci Campos
Diabetes mellitus (DM) is among the top ten causes of death worldwide. It is considered to be one of the major global epidemics of the 21st century, with a significant impact on public health budgets. DM is a metabolic disorder with multiple etiologies. Its pathophysiology is marked by dysfunction of pancreatic β-cells which compromises the synthesis and secretion of insulin along with resistance to insulin action in peripheral tissues (muscle and adipose). Subjects presenting insulin resistance in DM type 2 often also exhibit increased insulin secretion and hyperinsulinemia...
April 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29679277/the-role-of-mitochondrial-dna-damage-at-skeletal-muscle-oxidative-stress-on-the-development-of-type-2-diabetes
#5
Julia Matzenbacher Dos Santos, Denise Silva de Oliveira, Marcos Lazaro Moreli, Sandra Aparecida Benite-Ribeiro
Reduced cellular response to insulin in skeletal muscle is one of the major components of the development of type 2 diabetes (T2D). Mitochondrial dysfunction involves in the accumulation of toxic reactive oxygen species (ROS) that leads to insulin resistance. The aim of this study was to verify the involvement of mitochondrial DNA damage at ROS generation in skeletal muscle during development of T2D. Wistar rats were fed a diet containing 60% fat over 8 weeks and at day 14 a single injection of STZ (25 mg/kg) was administered (T2D-induced)...
April 20, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29679000/valsartan-alleviates-insulin-resistance-in-skeletal-muscle-of-chronic-renal-failure-rats
#6
Yang Wang, Ri-Bao Wei, Yue Yang, Ting-Yu Su, Meng-Jie Huang, Ping Li, Xiang-Mei Chen
BACKGROUND Studies on insulin resistance (IR) in chronic kidney disease (CKD) patients are rare, and its exact mechanism remains unclear. In this study, we explored the molecular mechanism of IR with chronic renal failure (CRF) and interventions to alleviate IR in patients with CRF. MATERIAL AND METHODS In vivo and in vitro models of CRF were established by 5/6 nephrectomy and urea stimulation C2C12 cells, respectively. Based on the CRF model, angiotensin II (Ang II) and valsartan groups were established to observe the effect of drug intervention on IR...
April 21, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29677194/combined-intervention-of-swimming-plus-metformin-ameliorates-the-insulin-resistance-and-impaired-lipid-metabolism-in-murine-gestational-diabetes-mellitus
#7
Liping Huang, Pingping Yue, Xuefei Wu, Ting Yu, Yang Wang, Ji Zhou, Derun Kong, Keyang Chen
Gestational diabetes mellitus (GDM) has short- and long- term influence on pregnant women and fetus. Swimming, as an aerobic exercise, can effectively improve the blood glucose level in GDM, but the effect of mild swimming alone was not very substantial. Metformin, as an oral antidiabetic drug, has obvious hypoglycemic effect, and is economic also, but the long-term effect on pregnant women and fetus has not been completely clear. We hypothesize that combined intervention of mild swimming and low dose of metformin, may effectively reduce blood glucose, improve the pregnancy outcomes in GDM dams, but simultaneously avoiding the adverse effects caused by overdose of drug and impotence of mild swimming...
2018: PloS One
https://www.readbyqxmd.com/read/29675927/tributyltin-reduces-the-levels-of-serum-adiponectin-and-activity-of-akt-and-induces-metabolic-syndrome-in-male-mice
#8
Haotian Yan, Hao Guo, Dong Cheng, Ruirui Kou, Cuili Zhang, Jiliang Si
Tributyltin (TBT), a proven environmental obesogen, functions as a nanomolar agonist of the peroxisome proliferator activated receptor-γ (PPARγ). However, the adverse effects of TBT on metabolism are incompletely understood. In this study, male ICR mice were administered TBT (5 and 50 μg·kg- 1 ) by an intraperitoneal injection once every 3 days for 30 days from 28 days of age and bred for another 30 days after the last administration of TBT. We analyzed the effects of these exposures on the fat depot weights, serum lipid profile, serum leptin and adiponectin, hepatic lipid accumulation, and activity of AKT in the liver and skeletal muscle isolated from mice 8 mins after receiving an insulin injection...
April 20, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29671031/short-term-decreased-physical-activity-with-increased-sedentary-behaviour-causes-metabolic-derangements-and-altered-body-composition-effects-in-individuals-with-and-without-a-first-degree-relative-with-type-2-diabetes
#9
Kelly A Bowden Davies, Victoria S Sprung, Juliette A Norman, Andrew Thompson, Katie L Mitchell, Jason C G Halford, Jo A Harrold, John P H Wilding, Graham J Kemp, Daniel J Cuthbertson
AIMS/HYPOTHESIS: Low physical activity levels and sedentary behaviour are associated with obesity, insulin resistance and type 2 diabetes. We investigated the effects of a short-term reduction in physical activity with increased sedentary behaviour on metabolic profiles and body composition, comparing the effects in individuals with first-degree relatives with type 2 diabetes (FDR+ve) vs those without (FDR-ve). METHODS: Forty-five habitually active participants (16 FDR+ve [10 female, 6 male] and 29 FDR-ve [18 female, 11 male]; age 36 ± 14 years) were assessed at baseline, after 14 days of step reduction and 14 days after resuming normal activity...
April 18, 2018: Diabetologia
https://www.readbyqxmd.com/read/29670757/gastric-inhibitory-polypeptide-receptor-antagonist-skl-14959-suppressed-body-weight-gain-on-diet-induced-obesity-mice
#10
T Nakamura, H Tanimoto, Y Mizuno, M Okamoto, M Takeuchi, Y Tsubamoto, H Noda
Objective: Gastric inhibitory polypeptide plays a role in glucose and lipid metabolism and is associated with obesity and insulin resistance. The objective of this study is to confirm the anti-obesity effects of the gastric inhibitory polypeptide receptor antagonist, SKL-14959, on diet-induced obesity mice. Method: Diet-induced obesity mice at 20 weeks of age were administered with or without SKL-14959 for 96 d. Body weight and food intake were monitored throughout the experiment...
April 2018: Obesity Science & Practice
https://www.readbyqxmd.com/read/29669812/tankyrase-modulates-insulin-sensitivity-in-skeletal-muscle-cells-by-regulating-the-stability-of-glut4-vesicle-proteins
#11
Zhiduan Su, Vinita Deshpande, David E James, Jacqueline Stöckli
Tankyrase1 and 2, members of the poly(ADP-ribose) polymerase family, have previously been shown to play a role in insulin-mediated glucose uptake in adipocytes. However, their precise mechanism of action, and their role in insulin action in other cell types, such as myocytes, remains elusive. Treatment of differentiated L6 myotubes with the small molecule tankyrase inhibitor XAV939 resulted in insulin resistance as determined by impaired insulin-stimulated glucose uptake. Proteomic analysis of XAV939-treated myotubes identified down-regulation of several glucose transporter GLUT4 storage vesicle (GSV) proteins including RAB10, VAMP8, SORT1 and GLUT4...
April 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29669306/paternal-exercise-protects-mouse-offspring-from-high-fat-diet-induced-type-2-diabetes-risk-by-increasing-skeletal-muscle-insulin-signaling
#12
Danielle Krout, James N Roemmich, Amy Bundy, Rolando A Garcia, Lin Yan, Kate J Claycombe-Larson
Paternal obesity increases, while paternal exercise decreases, offspring obesity and type 2 diabetes (T2D) risk; however, no studies have determined whether a paternal high-fat (HF) diet and exercise interact to alter offspring body weight (BW), adiposity and T2D risk. Three-week-old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or an HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF-diet-fed dams. After weaning, male offspring were fed an NF or HF diet for an additional 3 months...
March 21, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29662006/hyperinsulinemia-promotes-esophageal-cancer-development-in-a-surgically-induced-duodeno-esophageal-reflux-murine-model
#13
Diletta Arcidiacono, Arben Dedja, Cinzia Giacometti, Matteo Fassan, Daniele Nucci, Simona Francia, Federico Fabris, Alice Zaramella, Emily J Gallagher, Mauro Cassaro, Massimo Rugge, Derek LeRoith, Alfredo Alberti, Stefano Realdon
Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux...
April 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29659527/anti-diabetic-effects-and-anti-inflammatory-effects-of-laminaria-japonica-and-hizikia-fusiforme-in-skeletal-muscle-in-vitro-and-in-vivo-model
#14
Sae-Ym Kang, Eunyoung Kim, Inhae Kang, Myoungsook Lee, Yunkyoung Lee
Laminaria japonica ( LJ ) and Hizikia fusiforme ( HF ) are brown seaweeds known to have various health-promoting effects. In this study, we investigated the anti-diabetic effects and possible mechanism(s) of LJ and HF by using both in vitro and in vivo models. C2C12 myotubes, mouse-derived skeletal muscle cells, treated with LF or HF extracts were used for the in vitro model, and muscle tissues from C57BL/6N mice fed a high-fat diet supplemented with 5% LF or HF for 16 weeks were used for the in vivo model...
April 16, 2018: Nutrients
https://www.readbyqxmd.com/read/29657112/high-expression-of-cpt1b-in-skeletal-muscle-in-metabolically-healthy-older-subjects
#15
C Bétry, E Meugnier, M Pflieger, G Grenet, S Hercberg, P Galan, E Kesse-Guyot, H Vidal, M Laville
AIM: Ageing is often associated with metabolic abnormalities such as insulin resistance, although some people remain metabolically healthy throughout their lives. The aim of this study was to gain more insight into metabolic health with increasing age. METHODS: Two groups of robust and of frail subjects, respectively, were identified based on a composite ageing indicator and recruited from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men and 12 women, aged 67±4 years, with similar anthropometric and metabolic characteristics at baseline (BMI: 24...
February 12, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29657085/structural-determinants-for-small-molecule-activation-of-skeletal-muscle-ampk-%C3%AE-2%C3%AE-2%C3%AE-1-by-the-glucose-importagog-sc4
#16
Kevin R W Ngoei, Christopher G Langendorf, Naomi X Y Ling, Ashfaqul Hoque, Swapna Johnson, Michelle C Camerino, Scott R Walker, Ylva E Bozikis, Toby A Dite, Ashley J Ovens, William J Smiles, Roxane Jacobs, He Huang, Michael W Parker, John W Scott, Mark H Rider, Richard C Foitzik, Bruce E Kemp, Jonathan B Baell, Jonathan S Oakhill
The AMP-activated protein kinase (AMPK) αβγ heterotrimer regulates cellular energy homeostasis with tissue-specific isoform distribution. Small-molecule activation of skeletal muscle α2β2 AMPK complexes may prove a valuable treatment strategy for type 2 diabetes and insulin resistance. Herein, we report the small-molecule SC4 is a potent, direct AMPK activator that preferentially activates α2 complexes and stimulates skeletal muscle glucose uptake. In parallel with the term secretagog, we propose "importagog" to define a substance that induces or augments cellular uptake of another substance...
April 7, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29656554/a-single-day-of-bed-rest-irrespective-of-energy-balance-does-not-affect-skeletal-muscle-gene-expression-or-insulin-sensitivity
#17
Marlou L Dirks, Francis B Stephens, Sarah R Jackman, Jesús Galera Gordo, David Machin, Richard M Pulsford, Luc Jc van Loon, Benjamin T Wall
NEW FINDINGS: What is the central question of this study? What are the initial metabolic and molecular events that underpin bed rest-induced skeletal muscle deconditioning, and what is the contribution of energy balance? What is the main finding and its importance? A single day of bed rest, irrespective of energy balance, did not lead to overt changes in skeletal muscle gene expression or insulin sensitivity. More than one day of physical inactivity is required to observe the insulin resistance and robust skeletal muscle transcriptional responses associated with bed rest and consequent alterations in energy balance...
April 15, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29656500/mitochondria-glycogen-and-lipid-droplets-in-skeletal-muscle-during-testosterone-treatment-and-strength-training-a-randomized-double-blinded-placebo-controlled-trial
#18
R C Jensen, L L Christensen, J Nielsen, H D Schrøder, T Kvorning, K Gejl, K Højlund, D Glintborg, M Andersen
Low testosterone levels in aging men are associated with insulin resistance. Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation are linked to insulin resistance in skeletal muscle. In this randomized, double-blinded, placebo-controlled study, we investigated the effects of six-month testosterone replacement therapy (TRT) and strength training (ST) on mitochondrial, glycogen, and lipid droplet (LD) content in skeletal muscle of aging men with subnormal bioavailable testosterone (BioT) levels...
April 15, 2018: Andrology
https://www.readbyqxmd.com/read/29656048/trunk-muscle-quality-assessed-by-computed-tomography-association-with-adiposity-indices-and-glucose-tolerance-in-men
#19
Alexandre Maltais, Natalie Alméras, Isabelle Lemieux, Angelo Tremblay, Jean Bergeron, Paul Poirier, Jean-Pierre Després
BACKGROUND/OBJECTIVES: Thigh muscle attenuation measured by computed tomography (CT) has been shown to be a reliable and useful index of skeletal muscle fat infiltration. Thigh muscle fat content assessed by CT has been linked to obesity and type 2 diabetes and is a correlate of insulin resistance in sedentary individuals. However, as measurement of mid-thigh fat content requires the assessment of another region of interest beyond the usual abdominal scan required to measure levels of visceral and subcutaneous abdominal adipose tissue, this study aimed at testing the hypothesis that skeletal muscle fat measured from a single abdominal scan (L4 -L5 ) would also provide information relevant to the estimation of muscle fat infiltration as it relates to cardiometabolic risk...
April 12, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29652108/skeletal-muscle-specific-overexpression-of-heat-shock-protein-72-improves-skeletal-muscle-insulin-stimulated-glucose-uptake-but-does-not-alter-whole-body-metabolism
#20
Jps Marshall, E Estevez, H L Kammoun, E J King, C R Bruce, B G Drew, H Qian, P Illiades, P Gregorevic, M A Febbraio, D C Henstridge
AIMS: The induction of heat shock protein 72 (Hsp72) via heating, genetic manipulation or by pharmacological activation is metabolically protective in the setting of obesity-induced insulin resistance across mammalian species. In this study, we set out to determine whether the overexpression of Hsp72, specifically in skeletal muscle, can protect against high-fat diet (HFD)-induced obesity and insulin resistance. MATERIALS AND METHODS: An Adeno-Associated Viral vector (AAV) designed to overexpress Hsp72 in skeletal muscle only, was used to study the effects of increasing Hsp72 levels on various metabolic parameters...
April 13, 2018: Diabetes, Obesity & Metabolism
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