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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
#1
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
#2
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
#3
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
#4
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
#5
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. We demonstrated that ANGII-100-infused rats exhibited the phenotypic features of non-obese insulin resistance syndrome, including hypertension, impaired glucose tolerance and insulin resistance of glucose uptake in the soleus muscle, whereas ANGII-500-treated rats exhibited diabetes-like symptoms, such as post-prandial hyperglycemia, impaired insulin secretion and hypertriglyceridemia...
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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(-) )...
October 7, 2016: 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
#12
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
#13
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
https://www.readbyqxmd.com/read/27550988/acute-resistance-exercise-induced-igf1-expression-and-subsequent-glut4-translocation
#14
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/27521895/-e-9-oxooctadec-10-en-12-ynoic-acid-from-ixora-brachiata-roxb-increases-glucose-uptake-in-l6-myotubes-by-activating-the-pi3k-pathway
#15
Chandni S Thakkar, Rajendra R Kshirsagar, Vinayak R Naik, Asit Ranjan Ghosh, V Vijayakumar, Arvind Saklani, Asha A Kulkarni-Almeida
In an attempt to discover new scaffolds for anti-diabetic activity from plants, we screened extracts from Ixora brachiata Roxb. for their effect on glucose uptake in L6 myotubes. The petroleum (PE) extract of the plant showed a significant increase in insulin stimulated glucose uptake by L6 myotubes. The bioactivity guided fractionation of the crude extract yielded a compound (E)-9-oxooctadec-10-en-12-ynoic acid (OEA). The compound induced a dose dependent increase in insulin stimulated glucose uptake in L6 myotubes with an EC50 of 22...
October 2016: Fitoterapia
https://www.readbyqxmd.com/read/27514712/altered-steroid-metabolism-and-insulin-signaling-in-pcos-endometria-impact-in-tissue-function
#16
Lorena Oróstica, Carlos Rosas, Francisca Plaza-Parrochia, Isis Astorga, Fernando Gabler, Víctor García, Carmen Romero, Margarita Vega
BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine/ metabolic disorder characterized by hyperandrogenemia and in most cases, by hyperinsulinemia in addition to obesity. Besides ovarian dysfunction, endometrial physiology is also disrupted since this tissue is highly dependent on the action of steroids; in case of conception cycles, high percentage of abortion is observed. Because of the endocrine/metabolic alterations, PCOS-women present high probability to develop hyperplasia and endometrial cancer, where an imbalance of cell proliferation/apoptosis processes is detected...
2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27441957/mulberry-morus-alba-l-fruit-extract-containing-anthocyanins-improves-glycemic-control-and-insulin-sensitivity-via-activation-of-amp-activated-protein-kinase-in-diabetic-c57bl-ksj-db-db-mice
#17
Kyung Ha Choi, Hyun Ah Lee, Mi Hwa Park, Ji-Sook Han
The effect of mulberry (Morus alba L.) fruit extract (MFE) on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes was evaluated. C57BL/Ksj-diabetic db/db mice were divided into three groups: diabetic control, rosiglitazone, and MFE groups. Blood glucose, plasma insulin, and intraperitoneal glucose were measured, and an insulin tolerance test was performed after MFE supplementation in db/db mice. In addition, the protein levels of various targets of insulin signaling were measured by western blotting...
August 2016: Journal of Medicinal Food
https://www.readbyqxmd.com/read/27387397/protective-effects-of-marein-on-high-glucose-induced-glucose-metabolic-disorder-in-hepg2-cells
#18
Baoping Jiang, Liang Le, Wei Zhai, Wenting Wan, Keping Hu, Peng Yong, Chunnian He, Lijia Xu, Peigen Xiao
BACKGROUND: Our previous study has shown that Coreopsis tinctoria increases insulin sensitivity and regulates hepatic metabolism in high-fat diet (HFD)-induced insulin resistance rats. However, it is unclear whether or not marein, a major compound of C. tinctoria, could improve insulin resistance. Here we investigate the effect and mechanism of action of marein on improving insulin resistance in HepG2 cells. METHODS: We investigated the protective effects of marein in high glucose-induced human liver carcinoma cell HepG2...
August 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27379837/traumatic-brain-injury-decreases-amp-activated-protein-kinase-activity-and-pharmacological-enhancement-of-its-activity-improves-cognitive-outcome
#19
Julia L Hill, Nobuhide Kobori, Jing Zhao, Natalia S Rozas, Michael J Hylin, Anthony N Moore, Pramod K Dash
Prolonged metabolic suppression in the brain is a well-characterized secondary pathology of both experimental and clinical traumatic brain injury (TBI). AMP-activated kinase (AMPK) acts as a cellular energy sensor that, when activated, regulates various metabolic and catabolic pathways to decrease ATP consumption and increase ATP synthesis. As energy availability after TBI is suppressed, we questioned if increasing AMPK activity after TBI would improve cognitive outcome. TBI was delivered using the electromagnetic controlled cortical impact model on male Sprague-Dawley rats (275-300 g) and C57BL/6 mice (20-25 g)...
October 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27317126/benefits-of-l-alanine-or-l-arginine-supplementation-against-adiposity-and-glucose-intolerance-in-monosodium-glutamate-induced-obesity
#20
Thiago R Araujo, Israelle N Freitas, Jean F Vettorazzi, Thiago M Batista, Junia C Santos-Silva, Maria L Bonfleur, Sandra L Balbo, Antonio C Boschero, Everardo M Carneiro, Rosane A Ribeiro
PURPOSE: L-alanine (Ala) and L-arginine (Arg) have been reported to regulate pancreatic β-cell physiology and to prevent body fat accumulation in diet-induced obesity. Here, we assessed growth and adiposity parameters, glucose tolerance, insulin secretion and the expression of insulin and nutrient-regulated proteins in monosodium glutamate (MSG)-obese mice supplemented with either Ala or Arg. METHODS: Male newborn C57Bl/6 mice received a daily subcutaneous injection of MSG or saline solution (CTL group), during the first 6 days of life...
June 17, 2016: European Journal of Nutrition
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