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AMPK energy metabolism

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https://www.readbyqxmd.com/read/29784647/regulation-of-rabgaps-involved-in-insulin-action
#1
REVIEW
Samaneh Mafakheri, Alexandra Chadt, Hadi Al-Hasani
Rab (Ras-related proteins in brain) GTPases are key proteins responsible for a multiplicity of cellular trafficking processes. Belonging to the family of monomeric GTPases, they are regulated by cycling between their active GTP-bound and inactive GDP-bound conformations. Despite possessing a slow intrinsic GTP hydrolysis activity, Rab proteins rely on RabGAPs (Rab GTPase-activating proteins) that catalyze GTP hydrolysis and consequently inactivate the respective Rab GTPases. Two related RabGAPs, TBC1D1 and TBC1D4 (=AS160) have been described to be associated with obesity-related traits and type 2 diabetes in both mice and humans...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29782205/nad-repletion-produces-no-therapeutic-effect-in-mice-with-respiratory-chain-complex-iii-deficiency-and-chronic-energy-deprivation
#2
Janne Purhonen, Jayasimman Rajendran, Saara Tegelberg, Olli-Pekka Smolander, Eija Pirinen, Jukka Kallijärvi, Vineta Fellman
Biosynthetic precursors of NAD+ can replenish a decreased cellular NAD+ pool and, supposedly via sirtuin (SIRT) deacetylases, improve mitochondrial function. We found decreased hepatic NAD+ concentration and downregulated biosynthesis in Bcs1lp.S78G knock-in mice with respiratory chain complex III deficiency and mitochondrial hepatopathy. Aiming at ameliorating disease progression via NAD+ repletion and improved mitochondrial function, we fed these mice nicotinamide riboside (NR), a NAD+ precursor. A targeted metabolomics verified successful administration and suggested enhanced NAD+ biosynthesis in the treated mice, although hepatic NAD+ concentration was unchanged at the end point...
May 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29777910/differentially-expressed-novel-alternatively-spliced-transcript-variant-of-tumor-suppressor-stk11-gene-in-mouse
#3
Hassan Mubarak Ishqi, Tarique Sarwar, Mohammed Amir Husain, Sayeed Ur Rehman, Mohammad Tabish
Serine/threonine kinase 11 (STK11) is a protein kinase that is encoded by Stk11 gene located on chromosome 19 and 10 in humans and mouse respectively. It acts as a master kinase of adenine monophosphate-activated protein kinase (AMPK) pathway that coordinates the regulation of cellular energy metabolism and cell division. STK11 exerts effect by activating more than 14 kinases including AMPK and AMPK-related kinases. It is also known to regulate cell polarity and acts as tumor suppressor. Alternative splicing of pre-mRNA is a mechanism which results in multiple transcript variants of a single gene...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29775996/interplay-between-adenylate-metabolizing-enzymes-and-amp-activated-protein-kinase
#4
REVIEW
Marcella Camici, Simone Allegrini, Maria Grazia Tozzi
Purine nucleotides are involved in a variety of cellular functions, such as energy storage and transfer, and signalling, in addition to being the precursors of nucleic acids and cofactors of many biochemical reactions. They can be generated through two separate pathways, the de novo biosynthesis pathway and the salvage pathway. De novo purine biosynthesis leads to the formation of IMP, from which the adenylate and guanylate pools are generated by two additional steps. The salvage pathways utilize hypoxanthine, guanine and adenine to generate the corresponding mononucleotides...
May 18, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29771428/ampk-regulates-energy-metabolism-through-the-sirt1-signaling-pathway-to-improve-myocardial-hypertrophy
#5
H-W Dong, L-F Zhang, S-L Bao
OBJECTIVE: We investigated the correlations of adenosine monophosphate-activated protein kinase (AMPK), Silence information regulator 1 (SIRT1) and energy metabolism with myocardial hypertrophy. MATERIALS AND METHODS: Myocardial hypertrophy experimental model was established via transverse aortic constriction (TAC)-induced myocardial hypertrophy and phenylephrine (PE)-induced hypertrophic myocardial cell culture. After activation of AMPK, the messenger ribonucleic acid (mRNA) expressions in myocardial tissue- and myocardial cell hypertrophy-related genes, atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC), were detected...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29753740/2-deoxy-d-glucose-increases-gfat1-phosphorylation-resulting-in-endoplasmic-reticulum-related-apoptosis-via-disruption-of-protein-n-glycosylation-in-pancreatic-cancer-cells
#6
Kousuke Ishino, Mitsuhiro Kudo, Wei-Xia Peng, Shoko Kure, Kiyoko Kawahara, Kiyoshi Teduka, Yoko Kawamoto, Taeko Kitamura, Takenori Fujii, Tetsushi Yamamoto, Ryuichi Wada, Zenya Naito
The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines. To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment. Eighty proteins showed differential expression and among these, proteins involved in phosphohexose metabolism were upregulated. Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels...
May 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29743983/chemotherapeutic-drugs-and-mitochondrial-dysfunction-focus-on-doxorubicin-trastuzumab-and-sunitinib
#7
REVIEW
Stefania Gorini, Antonella De Angelis, Liberato Berrino, Natalia Malara, Giuseppe Rosano, Elisabetta Ferraro
Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic-induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29739863/effects-of-high-fat-diet-and-ampk-modulation-on-the-regulation-of-whole-body-lipid-metabolism
#8
Milena Schonke, Julie Massart, Juleen R Zierath
Metabolic flexibility, the capacity to adapt to fuel availability for energy production, is crucial for maintaining whole-body energy homeostasis. An inability to adequately promote fatty acid utilization is associated with lipid accumulation in peripheral tissues and contributes to the development of insulin resistance. In vivo assays to quantify whole-body lipid oxidation in mouse models of insulin resistance are lacking. We describe a method for assessing whole-body fatty acid oxidation in vivo , as well as tissue-specific lipid uptake in conscious mice...
May 8, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29737267/role-of-ampk-in-diabetic-cardiovascular-complications-an-overview
#9
Ashutosh Kumar, Karthika Nellaiappan, Veera Ganesh Yerra
Macrovascular complications of diabetes like cardiovascular diseases appear to be one of the leading causes of mortality. Current therapies aimed at counteracting the adverse effects of diabetes on cardiovascular system are found to be inadequate. Hence, there is growing need in search of novel targets. Adenosine monophosphate activated protein kinase (AMPK) is one such promising target, as a plethora of evidences point to its cardioprotective role in pathological milieu like cardiac hypertrophy, atherosclerosis and heart failure...
May 7, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29716943/hepatic-glucose-metabolic-responses-to-digestible-dietary-carbohydrates-in-two-isogenic-lines-of-rainbow-trout
#10
X Song, L Marandel, M Dupont-Nivet, E Quillet, I Geurden, S Panserat
Rainbow trout ( Oncorhynchus mykiss ) was recognized as typical "glucose-intolerant" fish and poor dietary carbohydrate user. Our first objective was to test the effect of dietary carbohydrates itself (without modification of dietary protein intake) on hepatic glucose gene expression (taking into account of the paralogs. The second aim was to research if two isogenic trout lines had different responds to carbohydrate intake, showing one with a better use dietary carbohydrates. Thus, we used two isogenic lines of rainbow trout (named A32h and AB1h) fed with either high carbohydrate diet or low carbohydrate diet for 12 weeks...
May 1, 2018: Biology Open
https://www.readbyqxmd.com/read/29713651/novel-mechanisms-modulating-palmitate-induced-inflammatory-factors-in-hypertrophied-3t3-l1-adipocytes-by-ampk
#11
Naru Morita, Toshio Hosaka, Atsuko Kitahara, Toshitaka Murashima, Hirohisa Onuma, Yoshikazu Sumitani, Kazuto Takahashi, Toshiaki Tanaka, Takuma Kondo, Hitoshi Ishida
Objective: A growing body of evidence indicates that AMP-activated protein kinase (AMPK) contributes to not only energy metabolic homeostasis but also the inhibition of inflammatory responses. However, the underlying mechanisms remain unclear. To elucidate the role of AMPK, in this study, we observed the effects of AMPK activation on monocyte chemoattractant protein-1 (MCP-1) release in mature 3T3-L1 adipocytes. Methods: We observed signal transduction pathways regulating MCP-1, which increased in obese adipocytes, in an in vitro model of hypertrophied 3T3-L1 adipocytes preloaded with palmitate...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29705631/metabolic-switching-in-the-hypoglycemic-and-antitumor-effects-of-metformin-on-high-glucose-induced-hepg2-cells
#12
Yan Lv, Na Tian, Junsong Wang, Minghua Yang, Lingyi Kong
Metformin, a widely prescribed drug for the management of type 2 diabetes mellitus, has potential anticancer effect. Diabetes patients regularly taking metformin have been reported with decreased cancer risk and improved cancer prognosis in recent years. A cell model of high glucose induced HepG2 cells was conducted to mimic insulin resistance, and a 1 H NMR-based metabolomics approach in conjunction with molecular biology was performed to investigate the metabolic changes of high glucose induced HepG2 cells in response to different doses of metformin treatment and to study the differences and links between hypoglycemic and antitumor effects of metformin...
April 21, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29699638/increased-frequency-of-amp-activated-protein-kinase-positive-spinal-motor-neurons-after-sciatic-nerve-injury-in-a-mouse-model
#13
Bao Qi, Gui-Jun Cao, Qing-Wei Li, Guo-Wu Chen, Xiao Liang, Yu-Zhong Wang, Chun-Yang Meng
The role of AMP-activated protein kinase (AMPK) in the regulation of energy metabolism and the control of skeletal muscle regeneration post injury has been described previously. It remains unknown whether this metabolic sensor plays a role in the mechanism of axonal regeneration post injury. In this study, we used a sciatic nerve crushed mouse model to detect the expression of AMPK in sciatic nerve and spinal motor neurons at 1 week, 2 weeks and 3 weeks after injury by immunofluorescence staining. Electrophysiological and histopathological studies were used to confirm the nerve injury and regeneration...
May 2018: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/29693118/ido-decreases-glycolysis-and-glutaminolysis-by-activating-gcn2k-while-it-increases-fatty-acid-oxidation-by-activating-ahr-thus-preserving-cd4-t%C3%A2-cell-survival-and-proliferation
#14
Theodoros Eleftheriadis, Georgios Pissas, Vassilios Liakopoulos, Ioannis Stefanidis
It is generally hypothesized in the literature that indoleamine 2,3‑dioxygenase (IDO), by degrading L‑tryptophan along the kynurenine pathway, suppresses CD4+ T‑cell function by inducing apoptosis, inhibiting proliferation and promoting differentiation towards a regulatory phenotype. These effects are either accompanied or directly lead to alterations in cell metabolism. The present study evaluated the pathways that govern the effect of IDO on the utilization of the three main energy sources in CD4+ T‑cells...
April 16, 2018: International Journal of Molecular Medicine
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
#15
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/29688281/long-term-dietary-macronutrients-and-hepatic-gene-expression-in-aging-mice
#16
Rahul Gokarn, Samantha M Solon-Biet, Victoria C Cogger, Gregory J Cooney, Devin Wahl, Aisling C McMahon, James R Mitchell, Sarah J Mitchell, Christopher Hine, Rafael de Cabo, David Raubenheimer, Stephen J Simpson, David G Le Couteur
Nutrition influences both hepatic function and aging, but mechanisms are poorly understood. Here, the effects of lifelong, ad libitum-fed diets varying in macronutrients and energy on hepatic gene expression were studied. Gene expression was measured using Affymetrix mouse arrays in livers of 46 mice aged 15 months fed one of 25 diets varying in protein, carbohydrates, fat, and energy density from 3 weeks of age. Gene expression was almost entirely influenced by protein intake. Carbohydrate and fat intake had few effects on gene expression compared with protein...
April 23, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29656339/role-of-ampk-in-atherosclerosis-via-autophagy-regulation
#17
REVIEW
Hanxiao Ou, Chuhao Liu, Wenjie Feng, Xinwen Xiao, Shengsong Tang, Zhongcheng Mo
Atherosclerosis is characterized by the accumulation of lipids and deposition of fibrous elements in the vascular wall, which is the primary cause of cardiovascular diseases. Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism that regulates multiple physiological processes, including lipid and glucose metabolism and the normalization of energy imbalances. Overwhelming evidence indicates that AMPK activation markedly attenuates atherosclerosis development. Autophagy inhibits cell apoptosis and inflammation and promotes cholesterol efflux and efferocytosis...
April 12, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29656110/targeting-hepatic-pyruvate-dehydrogenase-kinases-restores-insulin-signaling-and-mitigates-chrebp-mediated-lipogenesis-in-diet-induced-obese-mice
#18
Cheng-Yang Wu, Shih-Chia Tso, Jacinta L Chuang, Wen-Jun Gui, Mingliang Lou, Gaurav Sharma, Chalermchai Khemtong, Xiangbing Qi, R Max Wynn, David T Chuang
OBJECTIVE: Mitochondrial pyruvate dehydrogenase kinases 1-4 (PDKs1-4) negatively regulate activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation. PDKs play a pivotal role in maintaining energy homeostasis and contribute to metabolic flexibility by attenuating PDC activity in various mammalian tissues. Cumulative evidence has shown that the up-regulation of PDK4 expression is tightly associated with obesity and diabetes. In this investigation, we test the central hypothesis that PDKs1-4 are a pharmacological target for lowering glucose levels and restoring insulin sensitivity in obesity and type 2 diabetes (T2D)...
March 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29644357/the-inhibitory-effect-of-manuka-honey-on-human-colon-cancer-hct-116-and-lovo-cell-growth-part-2-induction-of-oxidative-stress-alteration-of-mitochondrial-respiration-and-glycolysis-and-suppression-of-metastatic-ability
#19
Sadia Afrin, Francesca Giampieri, Massimiliano Gasparrini, Tamara Y Forbes-Hernández, Danila Cianciosi, Patricia Reboredo-Rodriguez, Piera Pia Manna, Jiaojiao Zhang, Josè L Quiles, Maurizio Battino
Despite its high content of phenolic compounds, the chemopreventive activity of Manuka honey (MH) is still elusive. The aim of the present work was to evaluate the effects of MH on oxidative stress, antioxidant enzymes, cellular metabolism and the metastatic ability in HCT-116 and LoVo cells, paying particular attention to the molecular mechanisms involved. We observed a strong induction of oxidative stress after MH treatment since it augmented the accumulation of reactive oxygen species and increased the damage to proteins, lipids and DNA...
April 12, 2018: Food & Function
https://www.readbyqxmd.com/read/29643469/snf1-ampk-is-involved-in-the-mitotic-spindle-alignment-in-saccharomyces-cerevisiae
#20
Farida Tripodi, Roberta Fraschini, Monica Zocchi, Veronica Reghellin, Paola Coccetti
Before anaphase onset, budding yeast cells must align the mitotic spindle parallel to the mother-bud axis to ensure proper chromosome segregation. The protein kinase Snf1/AMPK is a highly conserved energy sensor, essential for adaptation to glucose limitation and in response to cellular stresses. However, recent findings indicate that it plays important functions also in non-limiting glucose conditions. Here we report a novel role of Snf1/AMPK in the progression through mitosis in glucose-repressing condition...
April 11, 2018: Scientific Reports
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