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https://www.readbyqxmd.com/read/29792552/immobilization-rapidly-induces-thioredoxin-interacting-protein-txnip-gene-expression-together-with-insulin-resistance-in-rat-skeletal-muscle
#1
Emi Kawamoto, Keigo Tamakoshi, Song-Gyu Ra, Hiroyuki Masuda, Kentaro Kawanaka
Acute short-duration of disuse induces the development of insulin resistance for glucose uptake in rodent skeletal muscle. Since thioredoxin-interacting protein (TXNIP) has been implicated in the downregulation of insulin signaling and glucose uptake, we examined the possibility that muscle disuse rapidly induces insulin resistance via increased TXNIP mRNA and protein expression. Male Wistar rats were subjected to unilateral 6-hr hindlimb immobilization by plaster cast. At the end of this period, the soleus muscles from both immobilized and contralateral non-immobilized hindlimbs were excised and examined...
May 24, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29788824/activation-of-ampk-in-human-placental-explants-impairs-mitochondrial-function-and-cellular-metabolism
#2
Daphne Landau, Maricela Haghiac, Judi Minium, Yelenna Skomorovska-Prokvolit, Virtu Calabuig-Navarro, Perrie O'Tierney-Ginn
OBJECTIVE: Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor whose phosphorylation increases energy production. We sought to evaluate the placenta-specific effect of AMPK activation on the handling of nutrients required for fetal development. METHODS: Explants were isolated from term placenta of 29 women (pregravid body mass index: 29.1 ± 9.9 kg/m2 ) and incubated for 24 hours with 0 to 100 µmol/L resveratrol or 0 to 1 mmol/L of 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR)...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29785900/insulin-suppresses-the-ampk-signaling-pathway-to-regulate-lipid-metabolism-in-primary-cultured-hepatocytes-of-dairy-cows
#3
Xinwei Li, Yu Li, Hongyan Ding, Jihong Dong, Renhe Zhang, Dan Huang, Lin Lei, Zhe Wang, Guowen Liu, Xiaobing Li
Dairy cows with type II ketosis display hepatic fat accumulation and hyperinsulinemia, but the underlying mechanism is not completely clear. This study aimed to clarify the regulation of lipid metabolism by insulin in cow hepatocytes. In vitro, cow hepatocytes were treated with 0, 1, 10, or 100 nm insulin in the presence or absence of AICAR (an AMP-activated protein kinase alpha (AMPKα) activator). The results showed that insulin decreased AMPKα phosphorylation. This inactivation of AMPKα increased the gene and protein expression levels of carbohydrate responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), which downregulated the expression of lipogenic genes, thereby decreasing lipid biosynthesis...
May 2018: Journal of Dairy Research
https://www.readbyqxmd.com/read/29773885/metabolic-perturbations-of-post-load-hyperglycemia-vs-fasting-hyperglycemia
#4
Jing-Yi Lu, Jia-Hui Peng, Xiao-Jing Ma, Yi-Nan Zhang, Wei Zhu, Xing-Xing He, Ling-Wen Ying, Yu-Qian Bao, Jian Zhou, Wei-Ping Jia
There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling...
May 17, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29773845/aicar-inhibits-nf%C3%AE%C2%BAb-dna-binding-independently-of-ampk-to-attenuate-lps-triggered-inflammatory-responses-in-human-macrophages
#5
Johannes Kirchner, Bernhard Brüne, Dmitry Namgaladze
5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an established pharmacological activator of AMP-activated protein kinase (AMPK). Both, AICAR and AMPK were reported to attenuate inflammation. However, AICAR is known for many AMPK-independent effects, although the mechanisms remain incompletely understood. Here we report a potent suppression of lipopolysaccharide (LPS)-induced inflammatory gene expression by AICAR in primary human macrophages, which occurred independently of its conversion to AMPK-activating 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29758325/high-glucose-up-regulated-vascular-smooth-muscle-et-b-receptors-via-inhibition-of-autophagy-in-rat-superior-mesenteric-arteries
#6
Yulong Chen, Hongmei Zhang, Huanhuan Liu, Ke Li, Min Jia, Xingli Su
Autophagy plays an important role in cardiovascular diseases (CVDs). High glucose (HG) up-regulates endothelin subtype B (ETB ) receptors in vascular smooth muscle cells (VSMCs). However, it is unclear as to whether autophagy is involved in HG -induced -up-regulation of ETB receptors in VSMCs. The present study was designed to examine the hypothesis that HG up-regulates ETB receptors by inhibiting autophagy in VSMCs. We studied HG -treated rat superior mesenteric artery (SMA) without endothelium in the presence and absence of AICAR, rapamycin or MHY1485 for 24 hours...
May 11, 2018: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29748634/gene-by-environment-interactions-that-disrupt-mitochondrial-homeostasis-cause-neurodegeneration-in-c-elegans-parkinson-s-models
#7
Hanna Kim, Rylee J Perentis, Guy A Caldwell, Kim A Caldwell
Parkinson's disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29730476/aicar-antiproliferative-properties-involve-the-ampk-independent-activation-of-the-tumor-suppressors-lats-1-and-2
#8
Chloé Philippe, Benoît Pinson, Jim Dompierre, Véronique Pantesco, Benoît Viollet, Bertrand Daignan-Fornier, Michel Moenner
AICAR (Acadesine) is a pharmacological precursor of purine nucleotide biosynthesis with anti-tumoral properties. Although recognized as an AMP mimetic activator of the protein kinase AMPK, the AICAR monophosphate derivative ZMP was also shown to mediate AMPK-independent effects. In order to unveil these AMPK-independent functions, we performed a transcriptomic analysis in AMPKα1/α2 double knockout murine embryonic cells. Kinetic analysis of the cellular response to AICAR revealed the up-regulation of the large tumor suppressor kinases (Lats) 1 and 2 transcripts, followed by the repression of numerous genes downstream of the transcriptional regulators Yap1 and Taz...
May 3, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29721631/multiple-chemo-genetic-interactions-between-a-toxic-metabolite-and-the-ubiquitin-pathway-in-yeast
#9
Delphine Albrecht, Hans C Hürlimann, Johanna Ceschin, Christelle Saint-Marc, Benoît Pinson, Bertrand Daignan-Fornier
AICAR is the precursor of ZMP, a metabolite with antiproliferative properties in yeast and human. We aim at understanding how AICAR (and its active form ZMP) affects essential cellular processes. In this work, we found that ZMP accumulation is synthetic lethal with a hypomorphic allele of the ubiquitin-activating enzyme Uba1. A search for gene-dosage suppressors revealed that ubiquitin overexpression was sufficient to restore growth of the uba1 mutant upon AICAR treatment, suggesting that the ubiquitin pool is critical for cells to cope with AICAR...
May 2, 2018: Current Genetics
https://www.readbyqxmd.com/read/29713279/astragaloside-iv-inhibits-triglyceride-accumulation-in-insulin-resistant-hepg2-cells-via-ampk-induced-srebp-1c-phosphorylation
#10
Chunyi Wang, Yan Li, Mengjiao Hao, Weimin Li
Objective: Insulin resistance (IR) is a risk factor for non-alcoholic fatty liver disease (NAFLD), which is characterized by lipid accumulation in hepatocytes. AMP-activated protein kinase (AMPK)-induced sterol regulatory element binding protein-1c (SREBP-1c) phosphorylation is crucial for proper regulation of lipid metabolism in the liver. Astragaloside IV (AST-IV) was found to decrease lipid accumulation in hepatocytes by activating AMPK, which is required to regulate lipid metabolism in liver tissue by inducing SREBP-1c phosphorylation...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29698445/evolutionary-convergence-in-the-biosyntheses-of-the-imidazole-moieties-of-histidine-and-purines
#11
Alberto Vázquez-Salazar, Arturo Becerra, Antonio Lazcano
BACKGROUND: The imidazole group is an ubiquitous chemical motif present in several key types of biomolecules. It is a structural moiety of purines, and plays a central role in biological catalysis as part of the side-chain of histidine, the amino acid most frequently found in the catalytic site of enzymes. Histidine biosynthesis starts with both ATP and the pentose phosphoribosyl pyrophosphate (PRPP), which is also the precursor for the de novo synthesis of purines. These two anabolic pathways are also connected by the imidazole intermediate 5-aminoimidazole-4-carboxamide ribotide (AICAR), which is synthesized in both routes but used only in purine biosynthesis...
2018: PloS One
https://www.readbyqxmd.com/read/29688769/il6-and-lif-mrna-expression-in-skeletal-muscle-is-regulated-by-ampk-and-the-transcription-factors-nfyc-zbtb14-and-sp1
#12
Carolina Nylén, Wataru Aoi, Ahmed M Abdelmoez, David G Lassiter, Leonidas S Lundell, Harriet Wallberg-Henriksson, Erik Näslund, Nicolas J Pillon, Anna Krook
AMPK controls glucose- and lipid- metabolism and modulates inflammatory responses to maintain metabolic and inflammatory homeostasis during low cellular energy levels. The AMPK activator 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) interferes with inflammatory pathways in skeletal muscle, but the mechanisms are undefined. We hypothesized that AMPK activation reduces cytokine mRNA levels by blocking transcription through one or several transcription factors. Three skeletal muscle models were used to study AMPK effects on cytokine mRNA: human skeletal muscle strips obtained from healthy men incubated in vitro, primary human muscle cells and rat L6 cells...
April 24, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29679571/metformin-ameliorates-tgf-%C3%AE-1-induced-osteoblastic-differentiation-of-human-aortic-valve-interstitial-cells-by-inhibiting-%C3%AE-catenin-signaling
#13
Liu Fayuan, Chu Chong, Wei Qinyu, Shi Jiawei, Li Huadong, Dong Nianguo
Osteoblastic differentiation of aortic valve interstitial cells (AVICs) is the central process in the development of calcific aortic valve disease (CAVD). Metformin is a widely used first-line antidiabetic drug, and recently, pleiotropic benefits of metformin beyond hypoglycemia have been reported in the cardiovascular system. Here, we examined the effect of metformin on the osteoblastic differentiation of human AVICs. Our results showed that metformin ameliorated TGF-β1-induced production of osteogenic proteins Runx2 and osteopontin as well as calcium deposition in the cultured human AVICs...
April 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29676471/vitamin-d3-regulates-steroidogenesis-in-granulosa-cells-through-amp-activated-protein-kinase-ampk-activation-in-a-mouse-model-of-polycystic-ovary-syndrome
#14
Shabnam Bakhshalizadeh, Fardin Amidi, Reza Shirazi, Maryam Shabani Nashtaei
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder in reproductive-aged women. Hormonal abnormality caused by steroidogenesis disturbances appears to be the main culprit of the clinical picture in PCOS. Vitamin D3 could regulate steroidogenesis in granulosa cells, but the mechanism of action of vitamin D3 on steroidogenesis remains unknown. AMP-activated protein kinase (AMPK) has a modulating role in steroid hormone production. We investigated the effect of vitamin D3 on steroidogenesis in cultured granulosa cells of dehydroepiandrosterone-induced PCOS mice and studied the involvement of AMPK signalling pathway in the current process...
April 20, 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29662080/involvement-of-amp-activated-protein-kinase-ampk-in-regulation-of-cell-membrane-potential-in-a-gastric-cancer-cell-line
#15
Lin Zhu, Xiao-Jian Yu, Sheng Xing, Feng Jin, Wei-Jun Yang
Membrane potential (Vmem ) is a key bioelectric property of non-excitable cells that plays important roles in regulating cell proliferation. However, the regulation of Vmem itself remains largely unexplored. We found that, under nutrient starvation, during which cell division is inhibited, MKN45 gastric cancer cells were in a hyperpolarized state associated with a high intracellular chloride concentration. AMP-activated protein kinase (AMPK) activity increased, and expression of cystic fibrosis transmembrane conductance regulator (CFTR) decreased, in nutrient-starved cells...
April 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29662023/serum-is-not-necessary-for-prior-pharmacological-activation-of-ampk-to-increase-insulin-sensitivity-of-mouse-skeletal-muscle
#16
Nicolas O Jørgensen, Jørgen F P Wojtaszewski, Rasmus Kjøbsted
Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats...
April 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29623826/targeting-ampk-in-diabetes-and-diabetic-complications-energy-homeostasis-autophagy-and-mitochondrial-health
#17
Y V Madhavi, Nikhil Gaikwad, Veera Ganesh Yerra, Anil Kumar Kalvala, Srinivas Nanduri, Ashutosh Kumar
Adenosine 5'-monophosphate activated protein kinase (AMPK) is a key enzymatic protein involved in linking the energy sensing to the metabolic manipulation. It is a serine/threonine kinase activated by several upstream kinases. AMPK is a heterotrimeric protein complex regulated by AMP, ADP, and ATP allosterically. AMPK is ubiquitously expressed in various tissues of the living system such as heart, kidney, liver, brain and skeletal muscles. Thus malfunctioning of AMPK is expected to harbor several human pathologies especially diseases associated with metabolic and mitochondrial dysfunction...
April 6, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29601873/homocysteine-up-regulates-et-b-receptors-via-suppression-of-autophagy-in-vascular-smooth-muscle-cells
#18
Yulong Chen, Hongmei Zhang, Huanhuan Liu, Ke Li, Xingli Su
The change of autophagy is implicated in cardiovascular diseases (CVDs). Homocysteine (Hcy) up-regulates endothelin type B (ETB ) receptors in vascular smooth muscle cells (VSMCs). However, it is unclear whether autophagy is involved in Hcy-induced-up-regulation of ETB receptors in VSMCs. The present study was designed to examine the hypothesis that Hcy up-regulates ETB receptors by inhibiting autophagy in VSMCs. Hcy treated the rat superior mesenteric artery (SMA) without endothelium in the presence and absence of AICAR, rapamycin or MHY1485 for 24 h...
March 27, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29581153/aicar-prevents-acute-olanzapine-induced-disturbances-in-glucose-homeostasis
#19
Natasha D Bush, Logan K Townsend, David C Wright
Olanzapine (OLZ) is an antipsychotic drug used in the treatment of schizophrenia. While effective in reducing psychoses, OLZ causes acute increases in blood glucose. The acute effects of OLZ on hyperglycaemia are likely caused by reductions in insulin secretion, insulin resistance and increased hepatic glucose production. 5'AMP-activated protein kinase (AMPK) is an energy sensor activated during exercise that can increase insulin sensitivity and insulin-independent glucose uptake in muscle. 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) is a pharmacological agent that, among other effects, can activate AMPK in vivo...
March 26, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29580989/amp-activated-protein-kinase-stabilizes-foxo3-in-primary-myotubes
#20
Anthony M J Sanchez, Robin Candau, Henri Bernardi
AMP-activated protein kinase (AMPK) is a critical enzyme in conditions of cellular energy deficit such as exercise, hypoxia or nutritional stress. AMPK is well known to regulate protein degradation pathways notably through FOXO-related axis. In this study, we investigated the implication of AMPK activation in FOXO3 expression and stability in skeletal muscle primary myotubes. First, time course and dose response studies revealed optimal AICAR treatment duration and dose in skeletal muscle cells. Then, experiments with cycloheximide treatment of primary myotubes highlighted that AICAR infusion extends FOXO3 protein half-life...
May 15, 2018: Biochemical and Biophysical Research Communications
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