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Insulin resistance AND mtor

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https://www.readbyqxmd.com/read/28934129/a-comprehensive-survey-of-the-roles-of-highly-disordered-proteins-in-type-2-diabetes
#1
Zhihua Du, Vladimir N Uversky
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with hyperglycemia (high blood sugar) related to either insulin resistance or insufficient insulin production. Among the various molecular events and players implicated in the manifestation and development of diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database has information on 34 human proteins experimentally shown to be related to the T2DM pathogenesis...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28923179/drugs-and-hyperglycemia-a-practical-guide
#2
REVIEW
Vandana Jain, Ronak Kumar Patel, Zaureen Kapadia, Sneha Galiveeti, Maryann Banerji, Lisel Hope
Drug-induced diabetes is one of the factors contributing to the increasing incidence of diabetes worldwide. This review considers the frequency, pathogenesis and treatment of drug-induced diabetes. Drugs that induce diabetes include hormonal therapy, especially glucocorticoids and androgen blockers, cardiovascular drugs, especially statins, beta-blockers and diuretics, antipsychotics, especially clozapine, olanzapine and quetiapine, antiretrovirals (protease inhibitors and non-reverse transcriptase inhibitors - NRTIs) and other drugs (mechanistic target of rapamycin inhibitors -mTORs, post organ transplantation drugs, tyrosine kinase inhibitors and interferon-alpha)...
October 2017: Maturitas
https://www.readbyqxmd.com/read/28919254/palmitic-acid-stimulates-energy-metabolism-and-inhibits-insulin-pi3k-akt-signaling-in-differentiated-human-neuroblastoma-cells-the-role-of-mtor-activation-and-mitochondrial-ros-production
#3
Erika Calvo-Ochoa, Karina Sánchez-Alegría, Cecilia Gómez-Inclán, Patricia Ferrera, Clorinda Arias
The high consumption of saturated lipids has been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance in peripheral tissues. However, how neurons develop insulin resistance in response to lipid overload is not fully understood. Here, we used cultured rat cortical neurons and differentiated human neuroblastoma cells to demonstrate that PA blocks insulin-induced metabolic activation, inhibits the activation of the insulin/PI3K/Akt pathway and activates mTOR kinase downstream of Akt...
September 15, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28917508/insulin-dependent-metabolic-and-inotropic-responses-in-the-heart-are-modulated-by-hydrogen-peroxide-from-nadph-oxidase-isoforms-nox2-and-nox4
#4
Benjamin Steinhorn, Juliano L Sartoretto, Andrea Sorrentino, Natalia Romero, Hermann Kalwa, E Dale Abel, Thomas Michel
RATIONALE: Hydrogen peroxide (H2O2) is a stable reactive oxygen species (ROS) that has long been implicated in insulin signal transduction in adipocytes. However, H2O2's role in mediating insulin's effects on the heart are unknown. OBJECTIVE: We investigated the role of H2O2 in activating insulin-dependent changes in cardiac myocyte metabolic and inotropic pathways. The sources of insulin-dependent H2O2 generation were also studied. METHODS AND RESULTS: In addition to the canonical role of insulin in modulating cardiac metabolic pathways, we found that insulin also inhibited beta adrenergic-induced increases in cardiac contractility...
September 14, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28860165/influence-of-nutrient-ingestion-on-amino-acid-transporters-and-protein-synthesis-in-human-skeletal-muscle-after-sprint-exercise
#5
Håkan Claes Rundqvist, Mona Esbjörnsson, Olav Rooyackers, Ted Osterlund, Marcus Moberg, William Apró, Eva Blomstrand, Eva Jansson
Nutrient ingestion is known to increase the exercise-induced stimulation of muscle protein synthesis following resistance exercise. Less is known about the effect of nutrients on muscle protein synthesis following sprint exercise. At two occasions separated by one month, twelve healthy subjects performed three 30-s sprints with 20-min rest between bouts. In randomized order, they consumed a drink with essential amino acids and maltodextrin (nutrient) or flavored water (placebo). Muscle biopsies were obtained 80 and 200 min after the last sprint and blood samples were taken repeatedly during the experiment...
August 31, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28843510/an-alternative-model-for-studying-age-associated-metabolic-complications-senescence-accelerated-mouse-prone-8
#6
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...
August 23, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28793771/systemic-perturbations-of-key-metabolites-in-type-2-diabetic-rats-treated-by-polyphenol-extracts-from-litchi-chinensis-seeds
#7
Shuli Man, Jiang Ma, Jingwen Yao, Jingxia Cui, Chunxia Wang, Yu Li, Long Ma, Fuping Lu
Our previous research obtained Litchi chinensis Sonn. seeds extract (LSE) which showed hypoglycaemic effects on type 2 diabetes (T2D) rats. In order to understand the detailed pathogenesis of diabetes intervened by LSE, the metabonomics strategy was used. As a result, LSE decreased the insulin resistance index and the levels of glucose in urine through elevating the mRNA level of insulin, while decreasing the expression of glucagon to enhance the function of the pancreas. Meanwhile, LSE regulated the glucose and fatty acid metabolisms via increasing the expression of glucose transporter (Glu) 2, Glu4, insulin receptor (IR), and IR substrate-2 (IRS2)...
September 6, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28766170/aegle-marmelos-differentially-affects-hepatic-markers-of-glycolysis-insulin-signalling-pathway-hypoxia-and-inflammation-in-hepg2-cells-grown-in-fructose-versus-glucose-rich-environment
#8
H Aggarwal, J Nair, P Sharma, R Sehgal, U Naeem, P Rajora, R Mathur
Fructose consumption is responsible for the onset of insulin resistance (IR), and metabolic syndrome. It possesses no functional utility in body and its detrimental effects on hepatic metabolic milieu are beyond those produced by glucose. The need of the hour is to identify fructose-induced IR as an unique pathological state to be managed differentially. The effect of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of insulin resistance using HepG2 cells cultured in either fructose or glucose-rich environment is investigated...
August 1, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28759152/anthocyanins-from-purple-corn-ameliorated-tnf-%C3%AE-induced-inflammation-and-insulin-resistance-in-3t3-l1-adipocytes-via-activation-of-insulin-signaling-and-enhanced-glut4-translocation
#9
Diego Luna-Vital, Matthew Weiss, Elvira Gonzalez de Mejia
SCOPE: The aim was to compare the effect of an anthocyanin-rich extract from purple corn pericarp (PCW) and pure anthocyanins on adipogenesis, inflammation and insulin resistance in 3T3-L1 adipocytes on basal and inflammatory conditions. METHODS AND RESULTS: Preadipocytes (3T3-L1) were treated during differentiation with or without PCW. Differentiated adipocytes were treated either individually or in combination with tumor necrosis factor TNF-α and PCW, or pure C3G, Pg3G, P3G...
July 31, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28694093/functional-analyses-of-major-cancer-related-signaling-pathways-in-alzheimer-s-disease-etiology
#10
REVIEW
Jianping Guo, Ji Cheng, Brian J North, Wenyi Wei
Alzheimer's disease (AD) is an aging-related neurodegenerative disease and accounts for majority of human dementia. The hyper-phosphorylated tau-mediated intracellular neurofibrillary tangle and amyloid β-mediated extracellular senile plaque are characterized as major pathological lesions of AD. Different from the dysregulated growth control and ample genetic mutations associated with human cancers, AD displays damage and death of brain neurons in the absence of genomic alterations. Although various biological processes predominately governing tumorigenesis such as inflammation, metabolic alteration, oxidative stress and insulin resistance have been associated with AD genesis, the mechanistic connection of these biological processes and signaling pathways including mTOR, MAPK, SIRT, HIF, and the FOXO pathway controlling aging and the pathological lesions of AD are not well recapitulated...
July 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28674285/a-high-sucrose-and-high-fat-diet-induced-the-development-of-insulin-resistance-in-the-skeletal-muscle-of-bama-miniature-pigs-through-the-akt-glut4-pathway
#11
Yaqian Liu, Jifang Yuan, Lei Xiang, Yuqiong Zhao, Miaomiao Niu, Xin Dai, Hua Chen
A high sucrose and high fat (HSHF) diet induces insulin resistance (IR) and increased susceptibility to type 2 diabetes mellitus (T2DM), but the underlying mechanisms are poorly characterized. This study aimed to investigate the molecular mechanisms by which the HSHF diet impairs insulin sensitivity in Bama miniature pigs (sus scrofa domesticus). Twelve Bama miniature pigs were randomly assigned to the control diet (CD) group (n=6) or the HSHF group (n=6) for 6 months. Biochemical parameters were measured. Western blot, RT-qPCR and immunohistochemistry were used to profile the changes of protein expression, mRNA expression and glucose transporter 4 (GLUT4) expression in skeletal muscle tissues, respectively...
July 3, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28663372/muscle-hypertrophy-in-pre-diabetic-men-after-sixteen-weeks-of-resistance-training
#12
Charles A Stuart, Michelle L Lee, Mark A South, Mary E A Howell, Michael H Stone
Resistance training of healthy young men typically results in muscle hypertrophy and a shift in vastus lateralis composition away from type IIx fibers to an increase in IIa fiber content. Our previous studies of eight weeks of resistance training found many metabolic syndrome men and women paradoxically increased IIx fibers with a decrease in IIa fibers. To confirm the hypothesis that obese subjects might have muscle remodeling after resistance training very different from healthy lean subjects, we subjected a group of nine obese men volunteers to progressive resistance training for a total of sixteen weeks...
June 29, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28646031/metabolism-and-acetylation-contribute-to-leucine-mediated-inhibition-of-cardiac-glucose-uptake
#13
Edith Renguet, Audrey Ginion, Roselle Gélinas, Laurent Bultot, Julien Auquier, Isabelle Robillard Frayne, Caroline Daneault, Jean-Louis Vanoverschelde, Christine Des Rosiers, Louis Hue, Sandrine Horman, Christophe Beauloye, Luc Bertrand
High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells have suggested that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts...
August 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28634451/berberine-ameliorates-diabetes-associated-cognitive-decline-through-modulation-of-aberrant-inflammation-response-and-insulin-signaling-pathway-in-dm-rats
#14
Qingjie Chen, Ran Mo, Ninghua Wu, Xin Zou, Cai Shi, Jing Gong, Jingbin Li, Ke Fang, Dingkun Wang, Deshen Yang, Kaifu Wang, Juan Chen
Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer's disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC). Previously, anti-inflammation and hypoglycemic effects of berberine (BBr) have been described in peripheral tissues...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28590761/proteome-wide-adaptations-of-mouse-skeletal-muscles-during-a-full-month-in-space
#15
Georg Tascher, Thomas Brioche, Pauline Maes, Angèle Chopard, Donal O'Gorman, Guillemette Gauquelin-Koch, Stéphane Blanc, Fabrice Bertile
The safety of space flight is challenged by a severe loss of skeletal muscle mass, strength, and endurance that may compromise the health and performance of astronauts. The molecular mechanisms underpinning muscle atrophy and decreased performance have been studied mostly after short duration flights and are still not fully elucidated. By deciphering the muscle proteome changes elicited in mice after a full month aboard the BION-M1 biosatellite, we observed that the antigravity soleus incurred the greatest changes compared with locomotor muscles...
June 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28585197/human-protein-kinases-and-obesity
#16
REVIEW
Atilla Engin
The action of protein kinases and protein phosphatases is essential for multiple physiological responses. Each protein kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by association with other proteins. Protein kinases are classified by the target amino acid in their substrates. Some protein kinases can phosphorylate both serine/threonine, as well as tyrosine residues. This group of kinases has been known as dual specificity kinases. Unlike the dual specificity kinases, a heterogeneous group of protein phosphatases are known as dual-specificity phosphatases...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28574822/endoplasmic-reticulum-stress-induces-autophagy-and-apoptosis-while-inhibiting-proliferation-and-drug-resistance-in-multiple-myeloma-through-the-pi3k-akt-mtor-signaling-pathway
#17
Yun-Feng Fu, Xiao Liu, Meng Gao, Ya-Nan Zhang, Jing Liu
We investigated the effects of endoplasmic reticulum stress (ERS) on autophagy, proliferation, apoptosis, and drug resistance in multiple myeloma (MM). MM patients enrolled in our study (n = 268) were classified into sensitive and resistant groups based on chemotherapy efficacy, and their serum levels of β2-MG, albumin (ALB), lactic dehydrogenase (LDH), Ca2+ and hemoglobin were determined. In addition, human MM U266 and MOLP-2/R cells were divided into blank, tunicamycin (TM), TM + insulin-like growth factor-1 (IGF-1), and TM + rapamycin groups, and measured expression of ERS-related, PI3K/Akt/mTOR pathway-related, and autophagy-related mRNA and proteins...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28573460/brain-glp-1-igf-1-signaling-and-autophagy-mediate-exendin-4-protection-against-apoptosis-in-type-2-diabetic-rats
#18
Emanuel Candeias, Inês Sebastião, Susana Cardoso, Cristina Carvalho, Maria Sancha Santos, Catarina Resende Oliveira, Paula I Moreira, Ana I Duarte
Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD). Since impaired brain insulin signaling may constitute the crosslink between T2D and AD, its restoration may be potentially therapeutic herein. Accordingly, the insulinotropic anti-T2D drugs from glucagon-like peptide-1 (GLP-1) mimetics, namely, exendin-4 (Ex-4), could be a promising therapy...
June 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28566814/endocrine-responses-and-acute-mtor-pathway-phosphorylation-to-resistance-exercise-with-leucine-and-whey
#19
M T Lane, T J Herda, A C Fry, M A Cooper, M J Andre, P M Gallagher
Leucine ingestion reportedly activates the mTOR pathway in skeletal muscle, contributing to a hypertrophy response. The purpose of the study was to compare the post-resistance exercise effects of leucine and whey protein supplementation on endocrine responses and muscle mTOR pathway phosphorylation. On visit 1, subjects (X±SD; n=20; age=27.8±2.8yrs) provided baseline blood samples for analysis of cortisol, glucose and insulin; a muscle biopsy of the vastus lateralis muscle to assess mTOR signaling pathway phosphorylation; and were tested for maximum strength on the leg press and leg extension exercises...
June 2017: Biology of Sport
https://www.readbyqxmd.com/read/28512156/effects-of-metformin-on-compensatory-pancreatic-%C3%AE-cell-hyperplasia-in-mice-fed-a-high-fat-diet
#20
Kazuki Tajima, Jun Shirakawa, Tomoko Okuyama, Mayu Kyohara, Shunsuke Yamazaki, Yu Togashi, Yasuo Terauchi
Metformin has been widely used for the treatment of type 2 diabetes. However, the effect of metformin on pancreatic β-cells remains controversial. In this study, we investigated the impacts of treatment with metformin on pancreatic β-cells in a mouse model fed a high-fat diet (HFD), which triggers adaptive β-cell replication. An 8-week treatment with metformin improved insulin resistance and suppressed the compensatory β-cell hyperplasia induced by HFD-feeding. In contrast, the increment in β-cell mass arising from 60 weeks of HFD-feeding was similar in mice treated with and those treated without metformin...
May 16, 2017: American Journal of Physiology. Endocrinology and Metabolism
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