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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
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
Bingxian Xie, Qiaoli Chen, Liang Chen, Yang Sheng, Hong Yu Wang, Shuai Chen
The AS160 is a Rab-GTPase activating protein (RabGAP) with several other functional domains, and its deficiency in mice or human patients lowers glucose transporter-4 (GLUT4) protein levels and causes severe insulin resistance. How its deficiency causes diminished GLUT4 proteins remains unknown. We found that 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...
August 23, 2016: Diabetes
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
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
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...
August 10, 2016: Current Pharmaceutical Design
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
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
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
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
Pragya Sharma, Edward B Arias, Gregory D Cartee
Akt substrate of 160 kDa (AS160) phosphorylation on Thr(642) and Ser(588) by Akt is essential for insulin's full effect on glucose transport. However, protein phosphorylation is determined by the balance of actions by kinases and phosphatases, and the specific phosphatase(s) controlling AS160 dephosphorylation is (are) unknown. Accordingly, we assessed roles of highly expressed skeletal muscle serine/threonine phosphatases (PP1, PP2A, PP2B, and PP2C) on AS160 dephosphorylation. Preliminary screening of candidate phosphatases used an AS160 dephosphorylation assay...
September 2016: Diabetes
Meenu Rohini Rajan, Elin Nyman, Preben Kjølhede, Gunnar Cedersund, Peter Strålfors
Insulin resistance is a major aspect of type 2 diabetes (T2D), which results from impaired insulin signaling in target cells. Signaling to regulate forkhead box protein O1 (FOXO1) may be the most important mechanism for insulin to control transcription. Despite this, little is known about how insulin regulates FOXO1 and how FOXO1 may contribute to insulin resistance in adipocytes, which are the most critical cell type in the development of insulin resistance. We report a detailed mechanistic analysis of insulin control of FOXO1 in human adipocytes obtained from non-diabetic subjects and from patients with T2D...
July 22, 2016: Journal of Biological Chemistry
Miguel Baena, Gemma Sangüesa, Alberto Dávalos, María-Jesús Latasa, Aleix Sala-Vila, Rosa María Sánchez, Núria Roglans, Juan Carlos Laguna, Marta Alegret
Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress...
2016: Scientific Reports
Hung-Wen Liu, Chu-Chun Wei, Yen-Ju Chen, Yun-An Chen, Sue-Joan Chang
SCOPE: An elevated intracellular lipid contents resulted from lipid oversupply links obesity to insulin resistance. Flavanol-rich lychee fruit extract, oligonol, exhibited anti-obesity property in vitro and in vivo; however, the effects of oligonol on peripheral lipid metabolism and insulin sensitivity have not been fully investigated. We hypothesized that oligonol alleviated insulin resistance via decreasing intracellular lipid contents in peripheral tissues. METHODS AND RESULTS: Dietary oligonol supplementation (20 or 200 mg/kg bw) reduced glucose and insulin levels, improved oral glucose tolerance, and suppressed inflammatory markers, MCP-1 and IL-6, in High-Fat diet (HFD) induced obese mice...
May 10, 2016: Molecular Nutrition & Food Research
Pianchou Gongpan, Yanting Lu, Fang Wang, Yuhui Xu, Wenyong Xiong
AS160 (TBC1D4) has been implicated in multiple biological processes. However, the role and the mechanism of action of AS160 in the regulation of cell proliferation remain unclear. In this study, we demonstrated that AS160 knockdown led to blunted cell proliferation in multiple cell types, including fibroblasts and cancer cells. The results of cell cycle analysis showed that these cells were arrested in the G1 phase. Intriguingly, this inhibition of cell proliferation and the cell cycle arrest caused by AS160 depletion were glucose independent...
July 2, 2016: Cell Cycle
Zhenwen Zhang, Penghua Fang, Biao He, Lili Guo, Johan Runesson, Ülo Langel, Mingyi Shi, Yan Zhu, Ping Bo
Our previous studies testified the beneficial effect of central galanin on insulin sensitivity of type 2 diabetic rats. The aim of the study was further to investigate whether central M617, a galanin receptor 1 agonist, can benefit insulin sensitivity. The effects of intracerebroventricular administration of M617 on insulin sensitivity and insulin signaling were evaluated in adipose tissues of type 2 diabetic rats. The results showed that central injection of M617 significantly increased plasma adiponectin contents, glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, GLUT4 mRNA expression levels, GLUT4 contents in plasma membranes, and total cell membranes of the adipose cells but reduced the plasma C-reactive protein concentration in nondiabetic and diabetic rats...
2016: Journal of Diabetes Research
I Papageorgiou, C Viglino, M-C Brulhart-Meynet, R W James, R Lerch, C Montessuit
We recently observed that free fatty acids impair the stimulation of glucose transport into cardiomyocytes in response to either insulin or metabolic stress. In vivo, fatty acids for the myocardium are mostly obtained from triglyceride-rich lipoproteins (chylomicrons and Very Low-Density Lipoproteins). We therefore determined whether exposure of cardiac myocytes to VLDL resulted in impaired basal and stimulated glucose transport. Primary adult rat cardiac myocytes were chronically exposed to VLDL before glucose uptake was measured in response to insulin or metabolic stress, provoked by the mitochondrial ATP synthase inhibitor oligomycin...
July 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Penghua Fang, Mei Yu, Biao He, Lili Guo, Xiaoli Huang, Guimei Kong, Mingyi Shi, Yan Zhu, Ping Bo, Zhenwen Zhang
Insulin resistance of skeletal muscle plays an important role in the pathogenesis of type 2 diabetes. Galanin, a 29/30-amino-acid neuropeptide, plays multiple biological actions, including anti-diabetic effects. Although recent results of our study showed that administration of galanin could mitigate insulin resistance by promoting glucose transporter 4 (GLUT4) expression and translocation in skeletal muscle of rats, there is no literature available regarding to the effect of type 1 of galanin receptors (GALR1) on insulin resistance in skeletal muscle of type 2 diabetic rats...
March 31, 2016: Mechanisms of Ageing and Development
Ulrike Lisewski, Clemens Koehncke, Nicola Wilck, Bastian Buschmeyer, Burkert Pieske, Torsten K Roepke
Hyperaldosteronism is associated with an increased prevalence of atrial fibrillation (AF). Mutations in KCNE3 have been associated with AF, and Kcne3(-/-) mice exhibit hyperaldosteronism. In this study, we used recently developed Kcne3(-/-) mice to study atrial electrophysiology with respect to development of aldosterone-dependent AF. In invasive electrophysiology studies, Kcne3(-/-) mice displayed a reduced atrial effective refractory period (AERP) and inducible episodes of paroxysmal AF. The cellular arrhythmogenic correlate for AF predisposition was a significant increase in atrial Kv currents generated by the micromolar 4-aminopyridine-sensitive Kv current encoded by Kv1...
July 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Laura Pentassuglia, Philippe Heim, Sonia Lebboukh, Christian Morandi, Lifen Xu, Marijke Brink
Nrg1β is critically involved in cardiac development and also maintains function of the adult heart. Studies conducted in animal models showed that it improves cardiac performance under a range of pathological conditions, which led to its introduction in clinical trials to treat heart failure. Recent work also implicated Nrg1β in the regenerative potential of neonatal and adult hearts. The molecular mechanisms whereby Nrg1β acts in cardiac cells are still poorly understood. In the present study, we analyzed the effects of Nrg1β on glucose uptake in neonatal rat ventricular myocytes and investigated to what extent mTOR/Akt signaling pathways are implicated...
May 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
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