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Insulin resistance AND mtor

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https://www.readbyqxmd.com/read/29128353/pyruvate-dehydrogenase-kinase-4-mediates-lipogenesis-and-contributes-to-the-pathogenesis-of-nonalcoholic-steatohepatitis
#1
Ming Zhang, Yujie Zhao, Zhen Li, Congying Wang
Nonalcoholic steatohepatitis (NASH) is a progressive disease and poses a high risk of severe liver damage. However, the pathogenesis of NASH is still unclear. Accumulation of lipid droplets and insulin resistance is the hallmark of NASH. Pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) plays key role in glucose metabolism via regulating the activity of pyruvate dehydrogenase complex (PDC). Here, we demonstrated a novel of PDK4 in NASH by regulating hepatic steatosis and insulin signaling pathway in methionine and choline deficient (MCD) diet induced NASH model...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29104874/akt-mtor-role-in-human-foetoplacental-vascular-insulin-resistance-in-diseases-of-pregnancy
#2
REVIEW
Roberto Villalobos-Labra, Luis Silva, Mario Subiabre, Joaquín Araos, Rocío Salsoso, Bárbara Fuenzalida, Tamara Sáez, Fernando Toledo, Marcelo González, Claudia Quezada, Fabián Pardo, Delia I Chiarello, Andrea Leiva, Luis Sobrevia
Insulin resistance is characteristic of pregnancies where the mother shows metabolic alterations, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), or abnormal maternal conditions such as pregestational maternal obesity (PGMO). Insulin signalling includes activation of insulin receptor substrates 1 and 2 (IRS1/2) as well as Src homology 2 domain-containing transforming protein 1, leading to activation of 44 and 42 kDa mitogen-activated protein kinases and protein kinase B/Akt (Akt) signalling cascades in the human foetoplacental vasculature...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29100507/inhibition-of-pi3k-akt-mtor-overcomes-cisplatin-resistance-in-the-triple-negative-breast-cancer-cell-line-hcc38
#3
Katharina Gohr, Alexandra Hamacher, Laura H Engelke, Matthias U Kassack
BACKGROUND: Widely established targeted therapies directed at triple negative breast cancer (TNBC) are missing. Classical chemotherapy remains the systemic treatment option. Cisplatin has been tested in TNBC but bears the disadvantage of resistance development. The purpose of this study was to identify resistance mechanisms in cisplatin-resistant TNBC cell lines and select targeted therapies based on these findings. METHODS: The TNBC cell lines HCC38 and MDA-MB231 were subjected to intermittent cisplatin treatment resulting in the 3...
November 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29099264/co-targeting-pi3k-mtor-and-igf1r-with-small-molecule-inhibitors-for-treating-undifferentiated-pleomorphic-sarcoma
#4
Caitlin D May, Sharon M Landers, Svetlana Bolshakov, XiaoYan Ma, Davis R Ingram, Christine M Kivlin, Kelsey L Watson, Ghadah A Al Sannaa, Angela D Bhalla, Wei-Lien Wang, Alexander J Lazar, Keila E Torres
Undifferentiated pleomorphic sarcomas (UPSs) are aggressive mesenchymal malignancies with no definitive cell of origin or specific recurrent genetic hallmarks. These tumors are largely chemoresistant; thus, identification of potential therapeutic targets is necessary to improve patient outcome. Previous studies demonstrated that high expression of activated protein kinase B (AKT) in patients with UPS corresponds to poor disease-specific survival. Here, we demonstrate that inhibiting phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling using a small molecule inhibitor reduced UPS cell proliferation and motility and xenograft growth; however, increased phosphorylation of insulin-like growth factor 1 receptor (IGF1R) indicated the potential for adaptive resistance following treatment through compensatory receptor activation...
October 3, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29074727/liver-reptin-ruvbl2-controls-glucose-and-lipid-metabolism-with-opposite-actions-on-mtorc1-and-mtorc2-signalling
#5
Joaquim Javary, Nathalie Allain-Courtois, Nicolas Saucisse, Pierre Costet, Capucine Heraud, Fadila Benhamed, Rémi Pierre, Corinne Bure, Nestor Pallares-Lupon, Marcio Do Cruzeiro, Catherine Postic, Daniela Cota, Pierre Dubus, Jean Rosenbaum, Samira Benhamouche-Trouillet
OBJECTIVE: The AAA+ ATPase Reptin is overexpressed in hepatocellular carcinoma and preclinical studies indicate that it could be a relevant therapeutic target. However, its physiological and pathophysiological roles in vivo remain unknown. This study aimed to determine the role of Reptin in mammalian adult liver. DESIGN AND RESULTS: We generated an inducible liver-specific Reptin knockout (Repin(LKO) ) mouse model. Following Reptin invalidation, mice displayed decreased body and fat mass, hypoglycaemia and hypolipidaemia...
October 26, 2017: Gut
https://www.readbyqxmd.com/read/29058763/s14g-humanin-alleviates-insulin-resistance-and-increases-autophagy-in-neurons-of-app-ps1-transgenic-mouse
#6
Kun Han, Ning Jia, Yi Zhong, Xiuli Shang
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by Aβ plaque deposition in the brain, which is related to the disorder of autophagosome maturation, transport and formation of autolysosome. Notably, abnormal insulin signaling is connected with cognitive dysfunction in AD. In this study, using APP/PS1 transgenic mice as AD model, we investigated the mechanism by which S14G-humanin (HNG) improved autophagy and insulin signaling in AD brain. Immunohistochemistry was used to determine the levels of mTOR and Aβ deposition, and Western blot analysis was used to determine IRS-1, IRS-1 pSEr636, ULK1, p62, LC3 I/LC3 II protein levels...
October 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29030784/anti-tnf-%C3%AE-antibody-alleviates-insulin-resistance-in-rats-with-sepsis-induced-stress-hyperglycemia
#7
W Qu, C Han, M Li, J Zhang, Z Jiang
PURPOSE: To explore the effects and mechanisms of anti-tumor necrosis factor-α (TNF-α) antibody on insulin resistance (IR) in rats with sepsis-induced stress hyperglycemia. METHODS: The sepsis-induced stress hyperglycemic rat model was constructed by cecal ligation and puncture combined with the intraperitoneal injection of lipopolysaccharide. The rats were randomly divided into six groups: normal control (NC) group, surgical rats (Cntl) group, high-dose anti-TNF-α antibody therapy (TNF, 6 mg/kg) group, low-dose anti-TNF-α antibody therapy (Tnf, 3 mg/kg) group, insulin therapy (INS) group, and INS + Tnf group...
October 13, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28990055/defective-insulin-signaling-and-the-protective-effects-of-dimethyldiguanide-during-follicular-development-in-the-ovaries-of-polycystic-ovary-syndrome
#8
Fan Wang, Shaobing Wang, Zhenghong Zhang, Qingqiang Lin, Yiping Liu, Yijun Xiao, Kaizhuan Xiao, Zhengchao Wang
It is established that the physiological effects of insulin are primarily mediated by the insulin signaling pathway. However, a defective insulin signaling is closely associated with the clinical manifestations of polycystic ovary syndrome (PCOS), which include excess androgen levels, insulin resistance and anovulation, and is involved in the pathophysiology of PCOS at the molecular level. Dimethyldiguanide (DMBG) has been widely employed to alleviate reproduction dysfunction in women with PCOS, however, the exact mechanism of this effect remains unclear...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28977849/endoplasmic-reticulum-stress-induces-autophagy-and-apoptosis-while-inhibiting-proliferation-and-drug-resistance-in-multiple-myeloma-through-the-pi3k-akt-mtor-signaling-pathway
#9
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), Ca(2+) 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...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28971834/differential-localisation-and-anabolic-responsiveness-of-mtor-complexes-in-human-skeletal-muscle-in-response-to-feeding-and-exercise
#10
Nathan Hodson, Chris McGlory, Sara Y Oikawa, Stewart Jeromson, Zhe Song, Markus A Ruegg, D Lee Hamilton, Stuart M Phillips, Andrew Philp
Mechanistic target of rapamycin (mTOR) resides as two complexes within skeletal muscle. mTOR complex 1 (mTORC1-Raptor positive) regulates skeletal muscle growth, whereas mTORC2 (Rictor positive) regulates insulin sensitivity. To examine the regulation of these complexes in human skeletal muscle, we utilised immunohistochemical analysis to study the localisation of mTOR complexes prior to and following protein-carbohydrate feeding (FED) and resistance exercise plus protein-carbohydrate feeding (EXFED) in unilateral exercise model...
September 27, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28944847/geniposide-promotes-autophagy-to-inhibit-insulin-resistance-in-hepg2-cells-via-p62-nf%C3%A2-%C3%AE%C2%BAb-glut%C3%A2-4
#11
Hongwei Jiang, Yujin Ma, Junqiang Yan, Jie Liu, Liping Li
Insulin resistance (IR) is known to be an important factor, which can lead to the onset of type 2 diabetes. Autophagy is a cellular process, which sequesters senescent or damaged proteins in autophagosomes for recycling of their products. Insulin and intracellular molecules, including mammalian target of rapamycin (mTOR), are well‑known inhibitors of autophagy. In patients with type 2 diabetes, the expression levels of glucose transporter 4 (GLUT‑4) in skeletal muscles are significantly decreased, indicating decreased glucose‑processing ability...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28934129/a-comprehensive-survey-of-the-roles-of-highly-disordered-proteins-in-type-2-diabetes
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
https://www.readbyqxmd.com/read/28793771/systemic-perturbations-of-key-metabolites-in-type-2-diabetic-rats-treated-by-polyphenol-extracts-from-litchi-chinensis-seeds
#18
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
#19
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
#20
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
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