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autophagy AND insulin

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https://www.readbyqxmd.com/read/30537019/lipophagy-in-nonliver-tissues-and-some-related-diseases-pathogenic-and-therapeutic-implications
#1
REVIEW
Kebing Zhou, Pingbo Yao, Jun He, Hong Zhao
Lipid autophagy (lipophagy) is defined as a selective autophagy process in which some intracellular lipid droplets are selectively degraded by autophagic lysosomes pathway. The occurrence of lipophagy was first discovered in liver tissues. Additionally, abundant evidence indicated that the occurrence of hepatic lipophagy has been implicated in many liver diseases including fatty liver diseases, nonalcoholic fatty liver diseases, liver fibrosis, and liver cirrhosis. However, recent studies suggested that hepatic lipophagy occurs not only in liver tissue but also in other nonliver tissues and cells...
December 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30532733/pleiotropic-effects-of-glp-1-and-analogs-on-cell-signaling-metabolism-and-function
#2
REVIEW
Jordan Rowlands, Julian Heng, Philip Newsholme, Rodrigo Carlessi
The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its "incretin effect" in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both in vitro and in vivo studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/30532260/effects-of-caloric-restriction-on-neuropathic-pain-peripheral-nerve-degeneration-and-inflammation-in-normometabolic-and-autophagy-defective-prediabetic-ambra1-mice
#3
Roberto Coccurello, Francesca Nazio, Claudia Rossi, Federica De Angelis, Valentina Vacca, Giacomo Giacovazzo, Patrizia Procacci, Valerio Magnaghi, Domenico Ciavardelli, Sara Marinelli
There is a growing interest on the role of autophagy in diabetes pathophysiology, where development of neuropathy is one of the most frequent comorbidities. We have previously demonstrated that neuropathic pain after nerve damage is exacerbated in autophagy-defective heterozygous Ambra1 mice. Here, we show the existence of a prediabetic state in Ambra1 mice, characterized by hyperglycemia, intolerance to glucose and insulin resistance. Thus, we further investigate the hypothesis that prediabetes may account for the exacerbation of allodynia and chronic pain and that counteracting the autophagy deficit may relieve the neuropathic condition...
2018: PloS One
https://www.readbyqxmd.com/read/30528240/salt-inducible-kinase-2-regulates-tfeb-and-is-required-for-autophagic-flux-in-adipocytes
#4
Florentina Negoita, Johanna Säll, Björn Morén, Karin Stenkula, Olga Göransson
Dysregulation of autophagy has been observed in obesity and type 2 diabetes. Salt-inducible kinase 2 (SIK2), a member of the AMPK-related kinase family, is downregulated in adipocytes from obese or insulin resistant individuals and was previously demonstrated to regulate autophagy in cancer and normal cell lines. The aim of this study was thus to investigate a potential role of SIK2 in the regulation of adipocyte autophagy. To do so, SIK2 siRNA silencing or SIKs pharmacological inhibition of SIK2 was employed in murine differentiated 3T3-L1 adipocytes and autophagic flux was monitored...
December 6, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30523026/foxo-transcription-factors-are-critical-regulators-of-diabetes-related-muscle-atrophy
#5
Brian T O'Neill, Gourav Bhardwaj, Christie M Penniman, Megan T Krumpoch, Pablo A Suarez Beltran, Katherine Klaus, Kennedy Poro, Mengyao Li, Hui Pan, Jonathan M Dreyfuss, K Sreekumaran Nair, C Ronald Kahn
Insulin deficiency and uncontrolled diabetes lead to a catabolic state with decreased muscle strength, contributing to disease-related morbidity. FoxO transcription factors are suppressed by insulin and thus are key mediators of insulin action. To study their role in diabetic muscle wasting, we created mice with muscle-specific triple knockout of FoxO1/3/4 and induced diabetes in these M-FoxO-TKO mice with streptozotocin (STZ). Muscle mass and myofiber area were decreased 20-30% in STZ-Diabetes mice due to increased ubiquitin-proteasome degradation and autophagy alterations, characterized by increased LC3 containing vesicles, and elevated levels of p-ULK1 and LC3-II...
December 6, 2018: Diabetes
https://www.readbyqxmd.com/read/30522623/metformin-associated-inflammation-levels-regulation-in-type-2-diabetes-mellitus-tuberculosis-coinfection-patients-a-case-report
#6
Bernadette Dian Novita, Endang Isbandiati Soediono, Jusak Nugraha
IFN-γ elevation is one of the indicators of successful treatment in active tuberculosis (TB) infection due to macrophage and Th-1 activation in inducing autophagy process. However, IL-10 also inhibits interferon-mediated mycobactericid activities by blocking IFN-γ; signaling pathways in autophagy. Therefore, ratio IFN-γ/IL-10 has to be greater than 1 (>1) then IFN-γ remains has anti-mycobacterium. Metformin (MET) is a potent combination drug to elevate anti-TB efficacy and able to regulate inflammation...
October 2018: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/30497501/gpr119-agonist-enhances-gefitinib-responsiveness-through-lactate-mediated-inhibition-of-autophagy
#7
Ji Hye Im, Keon Wook Kang, Sun Young Kim, Yoon Gyoon Kim, Yong Jin An, Sunghyouk Park, Byung Hwa Jeong, Song-Yi Choi, Jin-Sun Lee, Keon Wook Kang
BACKGROUND: Ligand-dependent activation of the G-protein coupled receptor 119 (GPR119) lowers blood glucose via glucose-dependent insulin secretion and intestinal glucagon-like peptide-1 production. However, the function of GPR119 in cancer cells has not been studied. METHODS: GPR119 expression was assessed by real-time qPCR and immunohistochemistry in human breast cancer cell lines and breast cancer tissues. Cell proliferation and cell cycle analyses were performed by Incucyte® live cell analysis system and flow cutometry, respectively...
November 29, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/30471281/emerging-role-of-unfolded-protein-response-upr-mediated-proteotoxic-apoptosis-in-diabetes
#8
REVIEW
Vivek Kumar Pandey, Alpana Mathur, Poonam Kakkar
Endoplasmic reticulum (ER) is a crucial single membrane organelle that acts as a quality control system for cellular proteins as it is intricately involved in their synthesis, folding and trafficking to the respective targets. Type 2 diabetes is characterized by enhanced blood glucose level that promotes insulin resistance and hampers cellular glucose metabolism. Hyperglycemia provokes mitochondrial ROS production and glycation of proteins which exert a tremendous load on ER for conventional refolding of misfolded/unfolded and nascent proteins that perturb ER homeostasis resulting in apoptotic cell death...
November 21, 2018: Life Sciences
https://www.readbyqxmd.com/read/30463689/inhibition-of-cyp2e1-attenuates-myocardial-dysfunction-in-a-murine-model-of-insulin-resistance-through-nlrp3-mediated-regulation-of-mitophagy
#9
Jun Ren, Zhaohui Pei, Xiyao Chen, Melissa J Berg, Khalid Matrougui, Qing-Hua Zhang, Yingmei Zhang
Insulin resistance leads to myocardial contractile dysfunction and deranged autophagy although the underlying mechanism or targeted therapeutic strategy is still lacking. This study was designed to examine the impact of inhibition of the cytochrome P450 2E1 (CYP2E1) enzyme on myocardial function and mitochondrial autophagy (mitophagy) in an Akt2 knockout model of insulin resistance. Adult wild-type (WT) and Akt2-/- mice were treated with the CYP2E1 inhibitor diallyl sulfide (100 mg/kg/d, i.p.) for 4 weeks...
January 2019: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/30444199/molecular-targets-anti-cancer-properties-and-potency-of-synthetic-indole-3-carbinol-derivatives
#10
Mojgan Karimabad Noroozi, Mehdi Mahmoodi, Abdolah Jafarzadeh, Ali Darekordi, Mohamad Reza Hajizadeh, Gholamhossein Hassanshahi
The indole-3-carbinol (I3C) displays anti-proliferative and anti-cancer activities against human cancer cells. Cellular proliferation is an important event associated with cancer development and continued progression. This manifest is described by altered expression and/or functions of cell cycle related proteins. The constitutive activation of many signal transduction pathways also stimulates cell growth. The immediate stages in tumor development are accompanied by a fibrogenic response and the progression of a hypoxic environment, is in favor of the survival and proliferatory functions of cancer stem cells...
November 16, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/30442237/mir-138-5p-affects-insulin-resistance-to-regulate-type-2-diabetes-progression-through-inducing-autophagy-in-hepg2-cells-by-regulating-sirt1
#11
Bingguo Luan, Caixia Sun
Insulin resistance (IR) is considered as a major factor of type 2 diabetes (T2D), which is seriously detrimental to human health. In our present study, we found that the expression of miR-138-5p was increased in the insulin-resistant HepG2 cells induced by TNF-α. Therefore, we hypothesized that miR-138-5p might play a regulatory role in the IR. To examine this hypothesis, HepG2 cells were transfected with miR-138-5p inhibitor. Silencing of miR-138-5p increased glucose uptake and glycogen synthesis of TNF-α-stimulated HepG2 cells and decreased glucose concentration in medium, suggesting that downregulation of miR-138-5p suppressed IR in HepG2 cells...
November 2018: Nutrition Research
https://www.readbyqxmd.com/read/30439604/celastrol-antagonizes-high-glucose-evoked-podocyte-injury-inflammation-and-insulin-resistance-by-restoring-the-ho-1-mediated-autophagy-pathway
#12
Xiaojiang Zhan, Caixia Yan, Yanbing Chen, Xin Wei, Jun Xiao, Lijuan Deng, Yuting Yang, Panlin Qiu, Qinkai Chen
Diabetic nephropathy (DN) contributes to end-stage renal disease and kidney dysfunction with a proverbial feature of podocyte injury. Inflammation and insulin resistance is recently implicated in the pathogenesis of diabetic kidney injury. Celastrol exerts critical roles in inflammatory diseases and injury progression. However, its function and mechanism in DN remains elusive. Here, celastrol dose-dependently restored podocyte viability under high glucose (HG) conditions, but with little cytotoxicity in podocyte...
December 2018: Molecular Immunology
https://www.readbyqxmd.com/read/30428342/autophagy-ablation-in-adipocytes-induces-insulin-resistance-and-reveals-roles-for-lipid-peroxide-and-nrf2-signaling-in-adipose-liver-crosstalk
#13
Jinjin Cai, Karla M Pires, Maroua Ferhat, Bhagirath Chaurasia, Márcio A Buffolo, Rana Smalling, Ashot Sargsyan, Donald L Atkinson, Scott A Summers, Timothy E Graham, Sihem Boudina
Autophagy is a homeostatic cellular process involved in the degradation of long-lived or damaged cellular components. The role of autophagy in adipogenesis is well recognized, but its role in mature adipocyte function is largely unknown. We show that the autophagy proteins Atg3 and Atg16L1 are required for proper mitochondrial function in mature adipocytes. In contrast to previous studies, we found that post-developmental ablation of autophagy causes peripheral insulin resistance independently of diet or adiposity...
November 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/30410750/intranasal-rapamycin-ameliorates-alzheimer-like-cognitive-decline-in-a-mouse-model-of-down-syndrome
#14
Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D Allan Butterfield, Marzia Perluigi, Fabio Di Domenico
Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/30400008/fam129a-regulates-autophagy-in-thyroid-carcinomas-in-an-oncogene-dependent-manner
#15
Bruno Heidi Nozima, Thais Biude Mendes, Gustavo José da Silva Pereira, Rodrigo Pinheiro Araldi, Edna Sadayo Miazato Iwamura, Soraya Soubhi Smaili, Gianna Maria Griz Carvalheira, Janete Maria Cerutti
We previously proposed that high expression of FAM129A can be used as a thyroid carcinoma biomarker in preoperative diagnostic exams of thyroid nodules. Here, we identify that FAM129A expression is increased under nutrient and growth factor depletion in a normal thyroid cell line (PCCL3), overlapping with increased expression of autophagy-related protein and inhibition of AKT/mTOR/p70S6K. Supplementation of insulin, TSH and serum to the medium was able to reduce the expression of both FAM129A and autophagy-related protein and reestablish the AKT/mTOR/p70S6K axis...
January 1, 2019: Endocrine-related Cancer
https://www.readbyqxmd.com/read/30390334/inhibitor-of-growth-4-inhibits-cell-proliferation-migration-and-induces-apoptosis-of-renal-cell-carcinoma-cells
#16
Jiping Sun, Liyi Xie, Jing Lv, Wenjing Zhang, Jia Lv, Yu Liang, Yingzhou Geng, Xudong Li
The inhibitor of growth 4 (ING4) is known as a tumor suppressor. The expressions of ING4 were markedly reduced in human renal clear cell carcinoma (ccRCC) tissues. However, the role of ING4 in renal cell carcinoma (RCC) remains unknown. The aim of the current study was to detect the ING4 expression level and its potential role in human RCC cell lines. Our results showed that ING4 was lowly expressed in human RCC cell lines compared with that in proximal tubular cell line. Ectopic overexpression of ING4 inhibited the proliferation, migration, and invasion properties, and as well as prevented epithelial-mesenchymal transition (EMT) phenotype of RCC cells...
November 2, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30386301/mtorc1-overactivation-as-a-key-aging-factor-in-the-progression-to-type-2-diabetes-mellitus
#17
REVIEW
Carlos Guillén, Manuel Benito
Type 2 Diabetes Mellitus (T2DM), a worldwide epidemics, is a progressive disease initially developing an insulin resistant state, with manifest pancreatic beta islet overwork and hyperinsulinemia. As the disease progresses, pancreatic β cells are overwhelmed and fails in their capacity to compensate insulin resistance. In addition, it is usually associated with other metabolic diseases such as hyperlipidemia, obesity and the metabolic syndrome. During the progression to T2DM there is a chronic activation of mTORC1 signaling pathway, which induces aging and acts as an endogenous inhibitor of autophagy...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/30386171/early-life-stress-and-epigenetics-in-late-onset-alzheimer-s-dementia-a-systematic-review
#18
REVIEW
Erwin Lemche
Involvement of life stress in Late-Onset Alzheimer's Disease (LOAD) has been evinced in longitudinal cohort epidemiological studies, and endocrinologic evidence suggests involvements of catecholamine and corticosteroid systems in LOAD. Early Life Stress (ELS) rodent models have successfully demonstrated sequelae of maternal separation resulting in LOAD-analogous pathology, thereby supporting a role of insulin receptor signalling pertaining to GSK-3beta facilitated tau hyper-phosphorylation and amyloidogenic processing...
November 2018: Current Genomics
https://www.readbyqxmd.com/read/30370550/effects-of-igfbp3-gene-silencing-mediated-inhibition-of-erk-mapk-signaling-pathway-on-proliferation-apoptosis-autophagy-and-cell-senescence-in-rats-nucleus-pulposus-cells
#19
Gang Chen, Xiaopeng Zhou, Zhengkuan Xu
OBJECTIVE: Disc degeneration is the common life-threatening disease characterized by flank pain. The gene expression of insulin-like growth factor binding protein 3 (IGFBP3) is increased in patients with disc degeneration, however, its mechanism is still unknown. This study aimed to investigate the influence of IGFBP3 gene silencing mediated inhibition of extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling on proliferation, apoptosis, autophagy, and cell senescence in rats nucleus pulposus (NP) cells...
October 28, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30362509/taurine-improves-low-level-inorganic-arsenic-induced-insulin-resistance-by-activating-ppar%C3%AE-mtorc2-signalling-and-inhibiting-hepatic-autophagy
#20
Ni Gao, Xiaofeng Yao, Liping Jiang, Lei Yang, Tianming Qiu, Zhidong Wang, Pei Pei, Guang Yang, Xiaofang Liu, Xiance Sun
Inorganic arsenic (iAs) is reportedly associated with the increased incidence of type 2 diabetes in the population. Here, we found that iAs exposure significantly decreased the expression of glycolytic genes and glycogen content and increased gluconeogenesis gene levels in C57/BL6J mice. The expression of peroxisome proliferator-activated receptor γ (PPARγ), and mechanistic target of rapamycin complex 2 (mTORC2) were decreased in the livers of iAs-treated mice. Furthermore, in iAs-treated HepG2 cells, we found that PPARγ agonist rosiglitazone (RGS) increased the expression of mTORC2, inhibited autophagy, and improved glucose metabolism...
October 26, 2018: Journal of Cellular Physiology
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