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Kentaro Oki, Edward B Arias, Makoto Kanzaki, Gregory D Cartee
5' AMP-activated protein kinase (AMPK) activation may be part of the exercise-induced process that enhances insulin sensitivity. Independent of exercise, acute prior treatment of skeletal muscles isolated from young rats with a pharmacological AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), causes subsequently improved insulin-stimulated glucose uptake (GU). However, efficacy of a single prior AICAR exposure on insulin-stimulated GU in muscles from old animals has not been studied...
March 8, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Leslie A Consitt, Gunjan Saxena, Yuriy Slyvka, Brian C Clark, Max Friedlander, Yizhu Zhang, Felicia V Nowak
Evidence suggests that paternal diet can predispose offspring to metabolic dysfunction. Despite this knowledge, little is known regarding the effects of paternal high-fat feeding on offspring insulin sensitivity. The purpose of this study was to investigate for the first time the effects of paternal high-fat feeding on whole-body and skeletal muscle insulin action in young and adult offspring. At 4 weeks of age, founder C57BL6/N males (F0) were fed a high-fat diet or control diet for 12 weeks and then bred with females on a control diet...
March 2018: Physiological Reports
Penghua Fang, Mei Yu, Wen Min, Dan Wan, Shiyu Han, Yizhi Shan, Rui Wang, Mingyi Shi, Zhenwen Zhang, Ping Bo
AIMS: Although baicalin could attenuate obesity-induced insulin resistance, the detailed mechanism of baicalin on glucose uptake has not been sufficiently explored as yet. The aim of this study was to survey if baicalin might facilitate glucose uptake and to explore its signal mechanisms in L6 myotubes. MATERIALS AND METHODS: L6 myotubes were treated with 100, 200, 400 μM baicalin for 6 h, 12 h and 24 h in this study. Then 2-NBDG and insulin signal protein levels in myotubes of L6 cells were examined...
March 1, 2018: Life Sciences
Xuzhu Lin, Lewan Parker, Emma Mclennan, Xinmei Zhang, Alan Hayes, Glenn McConell, Tara C Brennan-Speranza, Itamar Levinger
Uncarboxylated osteocalcin (ucOC) stimulates muscle glucose uptake in mice EDL and soleus muscles. However, whether ucOC also exerts a similar effect in insulin-stimulated muscles in a muscle type-specific manner is currently unclear. We aimed to test the hypothesis that, with insulin stimulation, ucOC per se has a greater effect on oxidative muscle compared with glycolytic muscle, and to explore the underlying mechanisms. Mouse (C57BL6, male 9-12 weeks) extensor digitorum longus (EDL) and soleus muscles were isolated and longitudinally split into halves...
February 9, 2018: Calcified Tissue International
A Aragón-Herrera, S Feijóo-Bandín, D Rodríguez-Penas, E Roselló-Lletí, M Portolés, M Rivera, M Bigazzi, D Bani, O Gualillo, J R González-Juanatey, F Lago
PURPOSE: Many evidences show that the hormone relaxin plays a pivotal role in the physiology and pathology of the cardiovascular system. This pleiotropic hormone exerts regulatory functions through specific receptors in cardiovascular tissues: in experimental animal models it was shown to induce coronary vasodilation, prevent cardiac damage induced by ischemia/reperfusion and revert cardiac hypertrophy and fibrosis. A tight relationship between this hormone and important metabolic pathways has been suggested, but it is at present unknown if relaxin could regulate cardiac metabolism...
February 6, 2018: Endocrine
Javier Lozano-Bartolomé, Gemma Llauradó, Manel Portero Otin, Antonio Altuna-Coy, Gemma Rojo-Martínez, Joan Vendrell, Rosa Jorba, Esther Rodríguez-Gallego, Matilde R Chacón
Context: The proinflammatory cytokine TNFα is a key player in insulin resistance (IR). While several miRNAs are believed to be involved in the development of adipose tissue (AT) IR, the role of miRNAs in the association between inflammation and IR is poorly understood. Objective: To investigate the expression profile of miR-181a-5p and miR-23a-3p in obesity and to study their role in TNFα-induced IR in adipocytes. Design: Two separate cohorts were employed...
February 1, 2018: Journal of Clinical Endocrinology and Metabolism
Aliz Szabo, Katalin Sumegi, Katalin Fekete, Eniko Hocsak, Balazs Debreceni, Gyorgy Setalo, Krisztina Kovacs, Laszlo Deres, Andras Kengyel, Dominika Kovacs, Jozsef Mandl, Miklos Nyitrai, Mark A Febbraio, Ferenc Gallyas, Balazs Sumegi
Mitochondria fragmentation destabilizes mitochondrial membranes, promotes oxidative stress and facilitates cell death, thereby contributing to the development and the progression of several mitochondria-related diseases. Accordingly, compounds that reverse mitochondrial fragmentation could have therapeutic potential in treating such diseases. BGP-15, a hydroxylamine derivative, prevents insulin resistance in humans and protects against several oxidative stress-related diseases in animal models. Here we show that BGP-15 promotes mitochondrial fusion by activating optic atrophy 1 (OPA1), a GTPase dynamin protein that assist fusion of the inner mitochondrial membranes...
January 26, 2018: Biochemical Pharmacology
Z Li, Y Zhu, C Li, Y Tang, Z Jiang, M Yang, C-L Ni, D Li, L Chen, W Niu
OBJECTIVE: A reduction in insulin-stimulated glucose uptake in skeletal muscles is a characteristic of insulin resistance and type 2 diabetes mellitus (T2DM). The glucagon-like peptide (GLP)-1 agonist liraglutide can reduce blood glucose levels in individuals with T2DM. However, its effect on insulin-induced glucose metabolism in the skeletal muscle of insulin resistance is unknown. We investigated the effects and action mechanisms of liraglutide on insulin resistance (IR) in the skeletal muscle cells treatment with palmitic acid (PA)...
January 27, 2018: Journal of Endocrinological Investigation
Björn Hansson, Sebastian Wasserstrom, Björn Moren, Vipul Periwal, Petter Vikman, Sam Cushman, Olga Göransson, Petter Storm, Karin Stenkula
To capture immediate cellular changes during diet-induced expansion of adipocyte cell volume and number, we characterized mature adipocytes during a short-term high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size distribution analysis using coulter counting. Insulin response in isolated adipocytes was monitored by glucose uptake assay and western blotting, and confocal microscopy was used to assess autophagic activity...
January 16, 2018: Journal of Molecular Endocrinology
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
Gabriela Silva, Cleber Ferraresi, Rodrigo Teixeira de Almeida, Mariana Lopes Motta, Thiago Paixão, Vinicius Oliveira Ottone, Ivana Alice Fonseca, Murilo Xavier Oliveira, Etel Rocha-Vieira, Marco Fabrício Dias-Peixoto, Elizabethe Adriana Esteves, Cândido Celso Coimbra, Fabiano Trigueiro Amorim, Flávio de Castro Magalhães
Obesity represents a continuously growing global epidemic and is associated with the development of type 2 diabetes mellitus. The etiology of type 2 diabetes is related to the resistance of insulin-sensitive tissues to its action leading to impaired blood glucose regulation. Photobiomodulation (PBM) therapy might be a non-pharmacological, non-invasive strategy to improve insulin resistance. It has been reported that PBM therapy in combination with physical exercise reduces insulin resistance. Therefore, the aim of this study was to investigate the effects of PBM therapy on insulin resistance in obese mice...
December 15, 2017: Lasers in Medical Science
Yumiko Takahashi, Yutaka Matsunaga, Yuki Tamura, Shin Terada, Hideo Hatta
Previous studies have shown that the short-term intake of a high-fat diet (HFD) impairs glucose metabolism. In this study, we investigated the influences of pre-exercise HFD intake for 3 d on post-exercise glycogen repletion in skeletal muscle in ICR mice. Mice received either an HFD (57% kcal from fat, 23% kcal from carbohydrate; HFD group) or standard laboratory chow (13% kcal from fat, 60% kcal from carbohydrate; Con group) for 3 d before exercise. Mice performed treadmill running at 25 m/min for 60 min and were orally administered a glucose (2 mg/g body weight) solution immediately after and at 60 min after exercise...
2017: Journal of Nutritional Science and Vitaminology
Xuzhu Lin, Lewan Parker, Emma Mclennan, Xinmei Zhang, Alan Hayes, Glenn McConell, Tara C Brennan-Speranza, Itamar Levinger
Emerging evidence suggests that undercarboxylated osteocalcin (ucOC) improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK), adenosine monophosphate-activated protein kinase (AMPK), and/or the mechanistic target of rapamycin complex 2 (mTORC2)-protein kinase B (AKT)-AKT substrate of 160 kDa (AS160) signaling cascade...
2017: Frontiers in Endocrinology
Penghua Fang, Lei Zhang, Mei Yu, Zhongqi Sheng, Mingyi Shi, Yan Zhu, Zhenwen Zhang, Ping Bo
The results of our and other's studies showed that activation of galanin receptor 1 could mitigate insulin resistance via promoting glucose transporter 4 (GLUT4) expression and translocation in the skeletal muscle of rats. But no literature are available regarding the effect of galanin receptor 2 (GALR2) on insulin resistance in skeletal muscle of type 2 diabetes. Herein, in this study we intended to survey the effect of GALR2 and its signal mechanisms in the mice with high fat diet-induced obese. The mice were intraperitoneally injected with vehicle, GALR2 agonist M1145 and antagonist M871 respectively once a day for continuous 21 days...
January 2018: Peptides
Zhiyong Liu, Nicole Bryant, Ravindran Kumaran, Alexandra Beilina, Asa Abeliovich, Mark R Cookson, Andrew B West
Human genetic studies implicate LRRK2 and RAB7L1 in susceptibility to Parkinson disease (PD). These two genes function in the same pathway, as knockout of Rab7L1 results in phenotypes similar to LRRK2 knockout, and studies in cells and model organisms demonstrate LRRK2 and Rab7L1 interact in the endolysosomal system. Recently, a subset of Rab proteins have been identified as LRRK2 kinase substrates. Herein, we find that Rab8, Rab10, and Rab7L1 must be membrane and GTP-bound for LRRK2 phosphorylation. LRRK2 mutations that cause PD including R1441C, Y1699C, and G2019S all increase LRRK2 phosphorylation of Rab7L1 four-fold over wild-type LRRK2 in cells, resulting in the phosphorylation of nearly one-third the available Rab7L1 protein in cells...
January 15, 2018: Human Molecular Genetics
Georgia Balsevich, Alexander S Häusl, Carola W Meyer, Stoyo Karamihalev, Xixi Feng, Max L Pöhlmann, Carine Dournes, Andres Uribe-Marino, Sara Santarelli, Christiana Labermaier, Kathrin Hafner, Tianqi Mao, Michaela Breitsamer, Marily Theodoropoulou, Christian Namendorf, Manfred Uhr, Marcelo Paez-Pereda, Gerhard Winter, Felix Hausch, Alon Chen, Matthias H Tschöp, Theo Rein, Nils C Gassen, Mathias V Schmidt
The co-chaperone FKBP5 is a stress-responsive protein-regulating stress reactivity, and its genetic variants are associated with T2D related traits and other stress-related disorders. Here we show that FKBP51 plays a role in energy and glucose homeostasis. Fkbp5 knockout (51KO) mice are protected from high-fat diet-induced weight gain, show improved glucose tolerance and increased insulin signaling in skeletal muscle. Chronic treatment with a novel FKBP51 antagonist, SAFit2, recapitulates the effects of FKBP51 deletion on both body weight regulation and glucose tolerance...
November 23, 2017: Nature Communications
E B Arias, H Wang, G D Cartee
Because greater Akt substrate of 160 kDa (AS160) phosphorylation has been reported in insulin-stimulated skeletal muscles without improved Akt activation several hours post-exercise, we hypothesized that prior exercise would result in attenuated AS160 dephosphorylation in insulin-stimulated rat skeletal muscle. Epitrochlearis muscles were isolated from rats that were sedentary (SED) or exercised 3 h earlier (3 h post-exercise; 3hPEX). Paired muscles were incubated with [(3)H]-2-deoxyglucose (2-DG) without insulin or with insulin...
November 10, 2017: Physiological Research
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-GLUT4HA) that contract in response to electrical pulse stimulation (EPS) and investigated molecular mechanisms regulating GLUT4HA EPS (60min, 20V, 1Hz, 24ms pulses at 976ms intervals) elicited a gain in surface GLUT4HA (GLUT4 translocation) comparably to insulin or 5-amino imidazole-4-carboxamide ribonucleotide (AICAR)...
October 31, 2017: American Journal of Physiology. Endocrinology and Metabolism
Hakam Alkhateeb, Esam Qnais
Insulin resistance in skeletal muscle is a feature associated with exposure to an excess of saturated fatty acids such as palmitate. Oleic acid has been shown to blunt palmitate-induced insulin resistance in muscle cells. However, there is no literature available regarding the effect of oleic acid on palmitate-induced insulin resistance in intact muscle. Therefore, this study investigated the effect of oleic acid on palmitate-induced insulin resistance in rat soleus muscle and its underlying mechanisms. For these purposes, oleic acid (1 mM) was administered for 12 h in the absence or presence of palmitate (2 mM)...
November 2017: Journal of Physiology and Biochemistry
Hung-Wen Liu, Yin-Ching Chan, Chu-Chun Wei, Yun-An Chen, Ming-Fu Wang, Sue-Joan Chang
Rodent animal models take at least 18months to develop aging phenotypes for researchers to investigate the mechanism of age-related metabolic complications. Senescence-accelerated mouse prone 8 (SAMP8) shortens the process of aging and may facilitate an alternative model for studying age-related insulin resistance. The short-lived strain SAMP8 and two long-lived strains SAM resistant 1 (SAMR1) mice and C57BL/6 mice at 12 (young) and 40weeks old (old) were used in the present study. Glucose tolerance test, histology and signaling pathways involved in lipid metabolism in adipose tissue and liver and key components of insulin signaling pathway in the skeletal muscle were determined in these three strains...
December 1, 2017: Experimental Gerontology
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