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Insulin resistance AND mtor

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https://www.readbyqxmd.com/read/29778908/mammalian-target-of-rapamycin-complex-2-signaling-in-obese-women-changes-after-bariatric-surgery
#1
Marcela Augusta de Souza Pinhel, Carolina Ferreira Nicoletti, Natalia Yumi Noronha, Bruno Affonso Parenti de Oliveira, Cristiana Cortes-Oliveira, Wilson Salgado, Wilson Araujo da Silva, Doroteia Rossi Silva Souza, Julio Sergio Marchini, Carla Barbosa Nonino
OBJECTIVES: After bariatric surgery, modifications to signaling pathway networks including those of the metabolic regulator called mammalian or mechanistic target of rapamycin (mTOR) may lead to molecular alterations related to energy source availability, systemic nutrients, and catabolic and anabolic cellular processes. This study aimed to identify gene expression changes with regard to the mTOR complex 2 subunit signaling pathway in obese patients before and after bariatric surgery...
March 21, 2018: Nutrition
https://www.readbyqxmd.com/read/29773580/resistin-inhibits-neuronal-autophagy-through-toll-like-receptor-4
#2
Jie Miao, Yacir Benomar, Sarah Al-Rifai, Ghislaine Poizat, Laure Riffault, Delphine Crepin, Mohammed Taouis
Autophagy is as a non-selective degradation pathway induced in energy-deprived cells and in non-starved cells by participating in cellular inflammatory responses mainly through the elimination of injured and aged mitochondria that constitute an important source of reactive oxygen species. We have previously reported that resistin/TLR4 signaling pathway induces inflammation and insulin resistance in neuronal cell. However, the impact of resistin-induced inflammation on neuronal autophagy is unknown. In the present study, we hypothesized that resistin-induced neuroinflammation could be attributed, at least partially, to the impairment of autophagy pathways in neuronal cells...
May 17, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29752839/the-role-of-mtor-in-ovarian-cancer-polycystic-ovary-syndrome-and-ovarian-aging
#3
REVIEW
Jin Liu, Dai-Chao Wu, Li-Hua Qu, Hong-Qing Liao, Mei-Xiang Li
The mammalian target of rapamycin, mTOR, is a serine-threonine protein kinase downstream of the phosphatidylinositol 3-kinase (PI3K)-AKT axis. The pathway can regulate cell growth, proliferation, and survival by activating ribosomal kinases. Recent studies have implicated the mTOR signaling pathway in ovarian neoplasms, polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). Preclinical investigations have demonstrated that the PI3K/AKT/mTOR pathway is frequently activated in the control of various ovarian functions...
May 12, 2018: Clinical Anatomy
https://www.readbyqxmd.com/read/29748034/ampk-induced-memory-improvements-in-the-diabetic-population-a-case-study
#4
Alicia Halikas, Kelly J Gibas
Diabetics in mid-life carry a 1.5 times higher risk of developing Alzheimer's disease than those diagnosed with diabetes (T2D) later in life [1]. Recent research points to accelerated cognitive decline within a range of 20%-50% for middle-aged diabetics as compared to non-diabetic populations [2,3]. Metabolic syndrome (MetS), a type 2 diabetes (T2D) precursor, is also linked to MCI and AD pathologies via hypo-metabolic brain circuitry that inhibits glucose metabolism and attenuates cognitive function [4]. Dysregulation of intracellular and extracellular signaling as mediated by the mTOR and AMPK pathways is the result...
April 27, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29738527/defensive-effect-of-microrna-200b-c-against-amyloid-beta-peptide-induced-toxicity-in-alzheimer-s-disease-models
#5
Sayuri Higaki, Masashi Muramatsu, Akio Matsuda, Kenji Matsumoto, Jun-Ichi Satoh, Makoto Michikawa, Shumpei Niida
MiRNA molecules are important post-transcriptional regulators of gene expression in the brain function. Altered miRNA profiles could represent a defensive response against the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). Endogenous miRNAs have lower toxic effects than other gene silencing methods, thus enhancing the expression of defensive miRNA could be an effective therapy. However, little is known about the potential of targeting miRNAs for the treatment of AD. Here, we examined the function of the miR-200 family (miR-200a, -141, -429, -200b, -200c), identified using miRNA microarray analysis of cortical tissue from Tg2576 transgenic mice...
2018: PloS One
https://www.readbyqxmd.com/read/29730286/vaspin-alleviates-myocardial-ischaemia-reperfusion-injury-via-activating-autophagic-flux-and-restoring-lysosomal-function
#6
Feihong Yang, Li Xue, Ziqi Han, Feng Xu, Shengchuan Cao, Shuai Dai, Baoshan Liu, Qiuhuan Yuan, Zheng Wang, Ping Guo, Yuguo Chen
Visceral adipose tissue-derived serine protease inhibitor (vaspin), as a secretory adipokine, was reported to exert a protective role on insulin resistance. Recent studies showed that serum vaspin level was downregulated in patients with coronary artery disease. However, whether vaspin exerted specific effects on myocardial injury remains unknown. In this study, we determined to explore the role of vaspin overexpression in myocardial ischaemia/reperfusion (I/R) injury and the underlying mechanisms. Our results showed that the systemic delivery of adeno-associated virus-vaspin to mice reduced myocardial infarct size and apoptosis, and improved cardiac function after reperfusion, accompanied with upregulated autophagic flux and restored lysosomal function in the ischaemic heart...
May 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29724916/inhibition-of-foxo1-transcription-factor-in-primary-human-adipocytes-mimics-the-insulin-resistant-state-of-type-2-diabetes
#7
Meenu R Rajan, Elin Nyman, Cecilia Brännmark, Charlotta S Olofsson, Peter Strålfors
Type 2 diabetes is characterized by insulin resistance in the expanding adipose tissue of obesity. The insulin resistance manifests in human adipocytes as system-wide impairment of insulin signalling. An exception is regulation of transcription factor FOXO1, which is phosphorylated downstream of mTORC2 and is therefore not exhibiting impaired response to insulin. However, the abundance, and activity, of FOXO1 is reduced by half in adipocytes from patients with diabetes. To elucidate the effect of reduced FOXO1 activity, we herein transduced human adipocytes with a dominant-negative construct of FOXO1 (DN-FOXO1)...
May 3, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29705631/metabolic-switching-in-the-hypoglycemic-and-antitumor-effects-of-metformin-on-high-glucose-induced-hepg2-cells
#8
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/29685622/early-dietary-restriction-in-rats-alters-skeletal-muscle-tuberous-sclerosis-complex-ribosomal-s6-and-mitogen-activated-protein-kinase
#9
Kara L Calkins, Shanthie Thamotharan, Yun Dai, Bo-Chul Shin, Satish C Kalhan, Sherin U Devaskar
Intrauterine growth restriction is linked to decreased lean body mass and insulin resistance. The mammalian target of rapamycin (mTOR) regulates muscle mass and glucose metabolism; however, little is known about maternal dietary restriction and skeletal muscle mTOR in offspring. We hypothesized that early dietary restriction would decrease skeletal muscle mass and mTOR in the suckling rat. To test this hypothesis, ab libitum access to food or dietary restriction during gestation followed by postnatal cross-fostering to a dietary-restricted or ad libitum-fed rat dam during lactation generated 4 groups: control (CON), intrauterine dietary restricted (IUDR), postnatal dietary restricted (PNDR), and IUDR+PNDR (IPDR)...
March 23, 2018: Nutrition Research
https://www.readbyqxmd.com/read/29604345/inflammation-insulin-signaling-and-cognitive-function-in-aged-app-ps1-mice
#10
Paul Denver, Andrew English, Paula L McClean
Cognitive dysfunction and neuroinflammation are typical in Alzheimer's disease (AD), but are also associated with normal aging, albeit less severely. Insulin resistance in the brain has been demonstrated in AD patients and is thought to be involved in AD pathophysiology. Using 15-18 month-old APP/PS1 mice, this study measured peripheral and central insulin signaling and sensitivity, inflammatory markers in brain and plasma and oxidative stress and synapse density in the brain. Novel object recognition, Morris water maze and reversal water maze tasks were performed to assess cognitive function in aged APP/PS1 mice and wild type littermates...
March 29, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29575997/1-25-oh-2d3-protects-trophoblasts-against-insulin-resistance-and-inflammation-via-suppressing-mtor-signaling
#11
Guanlin Li, Li Lin, Yan-Ling Wang, Huixia Yang
Gestational diabetes mellitus (GDM) is the primary cause of maternal and fetal morbidity and mortality. Insulin resistance (IR) is pivotal to GDM pathogenesis, and mammalian target of rapamycin (mTOR) is a critical regulator of GDM. An increasing amount of evidence indicates that vitamin D deficiency is a risk factor for GDM. However, there are few reports on the effect of IR on GDM placentas. The present study aims to verify that 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) can ameliorate trophoblast IR by suppressing mTOR signaling...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29570613/branched-chain-amino-acids-beyond-nutrition-metabolism
#12
REVIEW
Cunxi Nie, Ting He, Wenju Zhang, Guolong Zhang, Xi Ma
Branched chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), play critical roles in the regulation of energy homeostasis, nutrition metabolism, gut health, immunity and disease in humans and animals. As the most abundant of essential amino acids (EAAs), BCAAs are not only the substrates for synthesis of nitrogenous compounds, they also serve as signaling molecules regulating metabolism of glucose, lipid, and protein synthesis, intestinal health, and immunity via special signaling network, especially phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway...
March 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29550812/lack-of-clc-2-alleviates-high-fat-diet-induced-insulin-resistance-and-non-alcoholic-fatty-liver-disease
#13
Dongxia Fu, Haibin Cui, Yunna Zhang
BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. This study aims to investigate whether chloride channel 2 (ClC-2) is involved in high fat diet (HFD)-induced NAFLD and possible molecular mechanisms. METHODS: ClC-2 expression was liver-specifically downregulated using adeno-associated virus in C57BL/6 mice treated with a chow diet or HFD for 12 weeks. Peripheral blood and liver tissues were collected for biochemical and pathological estimation respectively...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29477657/berberine-induces-mir-373-expression-in-hepatocytes-to-inactivate-hepatic-steatosis-associated-akt-s6-kinase-pathway
#14
Chi Han Li, Shing Chun Tang, Chi Hin Wong, Yan Wang, Jian-Dong Jiang, Yangchao Chen
Berberine is a Chinese herbal medicine extracted from rhizoma coptidis that functions to improve insulin resistance, hyperlipidemia, hepatosteatosis and inflammation. Berberine can modify the activity of cell metabolism and signaling pathways by regulating expression of genes. However, the roles and effects of differential microRNA (miRNA) expression induced by berberine treatment are largely unexplored. It is believed that miRNAs expression modified by berberine contributes to its therapeutic effects to diseases such as hepatosteatosis and non-alcoholic fatty liver disease...
April 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29472733/androgen-interacts-with-exercise-through-the-mtor-pathway-to-induce-skeletal-muscle-hypertrophy
#15
Fanxing Zeng, Hua Zhao, Jingwen Liao
This study was designed to investigate the effects of exogenous androgen and resistance exercise on skeletal muscle hypertrophy and the role of the mammalian target of rapamycin (mTOR) signalling during the process. A total of 24 male Sprague-Dawley rats were randomly assigned to sham operation and dihydrotestosterone (DHT) implantation groups with subgroups subjected to sedentary conditions or resistance exercise (SHAM+SED, SHAM+EX, DHT+SED, and DHT+EX). The experimental procedure lasted for 10 days. The mRNA expression of androgen receptor (AR) and insulin-like growth factor I (IGF-I), the expression of myosin heavy chain (MHC), as well as the phosphorylation statuses of AR, mTOR, p70 ribosomal S6 kinase (p70S6K ), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) were determined in the white gastrocnemius muscle...
December 2017: Biology of Sport
https://www.readbyqxmd.com/read/29421605/impaired-insulin-signaling-and-spatial-learning-in-middle-aged-rats-the-role-of-ptp1b
#16
Gabriel Keine Kuga, Vitor Rosetto Muñoz, Rafael Calais Gaspar, Susana Castelo Branco Ramos Nakandakari, Adelino Sanchez Ramos da Silva, José Diego Botezelli, José Alexandre Curiacos de Almeida Leme, Ricardo José Gomes, Leandro Pereira de Moura, Dennys Esper Cintra, Eduardo Rochete Ropelle, José Rodrigo Pauli
The insulin and Brain-Derived Neurotrophic Factor (BDNF) signaling in the hippocampus promotes synaptic plasticity and memory formation. On the other hand, aging is related to the cognitive decline and is the main risk factor for Alzheimer's Disease (AD). The Protein-Tyrosine Phosphatase 1B (PTP1B) is related to several deleterious processes in neurons and emerges as a promising target for new therapies. In this context, our study aims to investigate the age-related changes in PTP1B content, insulin signaling, β-amyloid content, and Tau phosphorylation in the hippocampus of middle-aged rats...
April 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29387454/whole-genome-transcriptomic-insights-into-protective-molecular-mechanisms-in-metabolically-healthy-obese-african-americans
#17
Amadou Gaye, Ayo P Doumatey, Sharon K Davis, Charles N Rotimi, Gary H Gibbons
Several clinical guidelines have been proposed to distinguish metabolically healthy obesity (MHO) from other subgroups of obesity but the molecular mechanisms by which MHO individuals remain metabolically healthy despite having a high fat mass are yet to be elucidated. We conducted the first whole blood transcriptomic study designed to identify specific sets of genes that might shed novel insights into the molecular mechanisms that protect or delay the occurrence of obesity-related co-morbidities in MHO. The study included 29 African-American obese individuals, 8 MHO and 21 metabolically abnormal obese (MAO)...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29382663/long-noncoding-rna-lncshgl-recruits-hnrnpa1-to-suppress-hepatic-gluconeogenesis-and-lipogenesis
#18
Junpei Wang, Weili Yang, Zhenzhen Chen, Ji Chen, Yuhong Meng, Biaoqi Feng, Libo Sun, Lin Dou, Jian Li, Qinghua Cui, Jichun Yang
Mammalian genomes encode a huge number of long noncoding RNAs (lncRNAs) with unknown functions. This study determined the role and mechanism of a new lncRNA, lncRNA suppressor of hepatic gluconeogenesis and lipogenesis (lncSHGL), in regulating hepatic glucose/lipid metabolism. In the livers of obese mice and patients with nonalcoholic fatty liver disease, the expression levels of mouse lncSHGL and its human homologous lncRNA B4GALT1-AS1 were reduced. Hepatic lncSHGL restoration improved hyperglycemia, insulin resistance, and steatosis in obese diabetic mice, whereas hepatic lncSHGL inhibition promoted fasting hyperglycemia and lipid deposition in normal mice...
April 2018: Diabetes
https://www.readbyqxmd.com/read/29382127/the-implication-of-the-brain-insulin-receptor-in-late-onset-alzheimer-s-disease-dementia
#19
REVIEW
Jaume Folch, Miren Ettcheto, Oriol Busquets, Elena Sánchez-López, Rubén D Castro-Torres, Ester Verdaguer, Patricia R Manzine, Saghar Rabiei Poor, María Luisa García, Jordi Olloquequi, Carlos Beas-Zarate, Carme Auladell, Antoni Camins
Alzheimer's disease (AD) is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid β peptide (Aβ), which form senile plaques, neurofibrillary tangles (NFT) and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM) and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline...
January 29, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29378182/activation-of-mitochondrial-fusion-provides-a-new-treatment-for-mitochondria-related-diseases
#20
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...
April 2018: Biochemical Pharmacology
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