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https://www.readbyqxmd.com/read/30097599/autophagy-upregulation-as-a-possible-mechanism-of-arsenic-induced-diabetes
#1
Marzieh Zeinvand-Lorestani, Heibatullah Kalantari, Mohammad Javad Khodayar, Ali Teimoori, Najmaldin Saki, Akram Ahangarpour, Fakher Rahim, Soheila Alboghobeish
The key features of type 2 diabetes mellitus (T2DM) caused by high fat diet (HFD) in combination with arsenic (As) exposure (pronounced glucose intolerance despite a significant decrease in insulin resistance) are different from those expected for T2DM. Autophagy has been considered as a possible link between insulin resistance and obesity. Therefore in this study, we utilized autophagy gene expression profiling via real-time RT-PCR array analysis in livers of NMRI mice exposed to an environmentally relevant and minimally cytotoxic concentration of arsenite (50 ppm) in drinking water while being fed with a HFD for 20 weeks...
August 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30082607/role-and-cytotoxicity-of-amylin-and-protection-of-pancreatic-islet-%C3%AE-cells-from-amylin-cytotoxicity
#2
REVIEW
Yoshimitsu Kiriyama, Hiromi Nochi
Amylin, (or islet amyloid polypeptide; IAPP), a 37-amino acid peptide hormone, is released in response to nutrients, including glucose, lipids or amino acids. Amylin is co-stored and co-secreted with insulin by pancreatic islet β-cells. Amylin inhibits food intake, delays gastric emptying, and decreases blood glucose levels, leading to the reduction of body weight. Therefore, amylin as well as insulin play important roles in controlling the level of blood glucose. However, human amylin aggregates and human amylin oligomers cause membrane disruption, endoplasmic reticulum (ER) stress and mitochondrial damage...
August 6, 2018: Cells
https://www.readbyqxmd.com/read/30081744/the-becn1-bcl2-complex-regulates-insulin-secretion-and-storage-in-mice
#3
Kenta Kuramoto, Congcong He
Macroautophagy/autophagy abnormality has been recently associated with metabolic disorders, such as type 2 diabetes (T2D). However, the effect of autophagy activation in systemic energy metabolism was poorly understood. In our recent study, we demonstrated that autophagy plays different roles in distinct metabolic tissues, using an autophagy-hyperactive mouse model. In insulin-producing β cells, excess autophagy degrades insulin-containing vesicles (a process termed vesicophagy), resulting in decreased insulin contents and systemic glucose intolerance; whereas in insulin-responsive cells, activating autophagy decreases ER stress and improves insulin sensitivity...
August 6, 2018: Autophagy
https://www.readbyqxmd.com/read/30052487/transient-p53-inhibition-sensitizes-aged-white-adipose-tissue-for-beige-adipocyte-recruitment-by-blocking-mitophagy
#4
Wenyan Fu, Yang Liu, Christina Sun, Hang Yin
Aging of white adipose tissue (WAT) is associated with reduced insulin sensitivity, which contributes to whole-body glucose intolerance. WAT aging in mice impairs cold-induced beige adipocyte recruitment (beiging), which has been attributed to the senescence of adipose progenitor cells. Tumor suppressor p53 has also been implicated in WAT aging. However, whether p53-related cellular aging in mature white adipocytes is causative of age-impaired WAT beiging remains unknown. It is also unclear whether transient p53 inhibition can rescue WAT beiging...
July 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30052418/altered-processing-of-beta-amyloid-in-sh-sy5y-cells-induced-by-model-senescent-microglia
#5
Dafina Martinova Angelova, David Ronald Brown
The single greatest risk factor for neurodegenerative diseases is aging. Aging of cells such as microglia in the nervous system has an impact not only on the ability of those cells to function but also on cells they interact with. We have developed a model microglia system that recapitulates the dystrophic/senescent phenotype and we have combined this with the study of β-amyloid processing. The model is based on the observation that aged microglia have increased iron content. By overloading a human microglial cell line with iron we were able to change the secretory profile of the microglia...
July 27, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30048751/exercise-improves-glucose-uptake-in-murine-myotubes-through-the-ampk%C3%AE-2-mediated-induction-of-sestrins
#6
Tianyi Wang, Yanmei Niu, Sujuan Liu, Hairui Yuan, Xiaolei Liu, Li Fu
Exercise training increases insulin sensitivity. Over the past decades, considerable progress has been made in understanding the molecular basis for this important effect of physical exercise. However, the underlying mechanism is still not fully described. Recent studies have revealed that the stress responsive protein family Sestrins (SESNs) may play an important role in improving insulin sensitivity of skeletal muscle under exercise training. In this study, we aim to better understand the relationship between SESNs and AMPK in response to exercise training and the possible mechanism by which SESNs mediate glucose metabolism...
July 23, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/30047328/natural-products-modulating-autophagy-pathway-against-the-pathogenesis-of-diabetes-mellitus
#7
Linghuan Li, Jiameng Qi, Hanbing Li
Autophagy is a conserved, regulated cellular process for the degradation of abnormal proteins and disrupted organelles. Literature has described that dysregulation of autophagy is closely related to the pathogenesis of diabetes mellitus in processes such as impaired pancreatic β cells function, peripheral insulin resistance and diabetic complications. Emerging evidence indicates that natural products may possess anti-diabetic activity via regulation of autophagy. In this review, we summarize natural products targeting the pathogenesis of diabetes mellitus through the regulation of autophagy and underline possible mechanisms, providing potential drug candidates or therapies for the treatment of diabetes mellitus...
July 25, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/30047243/skeletal-muscle-autophagy-remains-responsive-to-hyperinsulinemia-and-hyperglycemia-at-higher-plasma-insulin-concentrations-in-insulin-resistant-mice
#8
Sarah E Ehrlicher, Harrison D Stierwalt, Sean A Newsom, Matthew M Robinson
Skeletal muscle autophagy is suppressed by insulin, but it is not clear if such suppression is altered with insulin resistance. We investigated if the inhibitory action of insulin on autophagy remains intact despite insulin resistance to glucose metabolism. C57BL/6J mice consumed either a low-fat (10% fat) diet as control or high-fat (60% fat) diet for 12 weeks to induce insulin resistance. Following a 5-hour fast, mice underwent either hyperinsulinemic-euglycemic, hyperinsulinemic-hyperglycemic, or saline infusion to test the effect of insulin on autophagy markers in the quadriceps muscle (n = 8-10 per diet and clamp condition)...
July 2018: Physiological Reports
https://www.readbyqxmd.com/read/30031229/cardiomyocyte-specific-knockout-of-endothelin-receptor-a-attenuates-obesity-cardiomyopathy
#9
Asli F Ceylan, Shuyi Wang, Machender R Kandadi, Jie Chen, Yinan Hua, Zhaohui Pei, Sreejayan Nair, Jun Ren
Endothelin (ET)-1 is implicated in the pathophysiology of cardiovascular diseases although its role in obesity anomalies has not been fully elucidated. This study was designed to examine the impact of ET-1 receptor A (ETA ) ablation on obesity-induced changes in cardiac geometry and contractile function, as well as the mechanisms involved with a focus on autophagy. Cardiomyocyte-specific ETA receptor knockout (ETAKO) and WT mice were fed either low-fat (10% calorie from fat) or high-fat (45% calorie from fat) diet for 24 weeks...
July 18, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/30018781/hiv-associated-cardiovascular-disease-importance-of-platelet-activation-and-cardiac-fibrosis-in-the-setting-of-specific-antiretroviral-therapies
#10
REVIEW
Jeffrey Laurence, Sonia Elhadad, Jasimuddin Ahamed
HIV infection is a risk factor for cardiovascular disease (CVD). This risk is accentuated by certain combination antiretroviral therapies (cARTs), independent of their effects on lipid metabolism and insulin sensitivity. We sought to define potential mechanisms for this association through systematic review of clinical and preclinical studies of CVD in the setting of HIV/cART from the English language literature from 1989 to March 2018. We used PubMed, Web of Knowledge and Google Scholar, and conference abstracts for the years 2015-March 2018...
2018: Open Heart
https://www.readbyqxmd.com/read/30017231/neuroprotective-effects-of-the-novel-glp-1-long-acting-analogue-semaglutide-in-the-mptp-parkinson-s-disease-mouse-model
#11
Liping Zhang, Lingyu Zhang, Lin Li, Christian Hölscher
Parkinson's disease (PD) is the second most common neurodegenerative disease, and there is no recognised therapy to cure it. Recently, it has been shown that treatments to improve insulin resistance in type 2 diabetes (T2DM) may be useful for PD patients. In previous studies, the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide showed good neuroprotective effects in animal models of PD. In addition, the GLP-1 mimetic exendin-4 has shown good protective effects in PD patients in a phase II clinical trial...
July 11, 2018: Neuropeptides
https://www.readbyqxmd.com/read/30008033/effects-of-insulin-like-growth-factor-1-on-endoplasmic-reticulum-stress-and-autophagy-in-rat-gastric-smooth-muscle-cells-cultured-at-different-glucose-concentrations-in-vitro
#12
Xue-Sen Fang, Mo-Han Zhang, Jun-Yu Guo, Zheng Jin
The purpose of the study was to observe changes in endoplasmic reticulum stress (ERS)- and autophagy-related proteins in gastric smooth muscle tissues of diabetic rats with gastroparesis, investigate the effect of insulin-like growth factor 1 (IGF-1) on ERS and autophagy in rat gastric smooth muscle cells cultured under different glucose concentrations, and explore the influence of IGF-1 on development of diabetic gastroparesis (DGP). After establishing a rat model of DGP, rats were divided into normal control (NC) and 6-week diabetic model (DM6W) groups...
July 14, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/30002135/opposing-effects-of-intracellular-versus-extracellular-adenine-nucleotides-on-autophagy-implications-for-%C3%AE-cell-function
#13
Tal Israeli, Yael Riahi, Ann Saada, Devorah Yefet, Erol Cerasi, Boaz Tirosh, Gil Leibowitz
AMPK-mTORC1 signaling senses nutrient availability, thereby regulating autophagy. Surprisingly, we found that, in β-cells, the AMPK activator 5-amino-4-imidazolecarboxamide ribofuranoside (AICAR) inhibited, rather than stimulated, autophagy. AICAR is an intermediate in the generation of inosine monophosphate, with subsequent conversion to other purine nucleotides. Adenosine regulated autophagy in a concentration-dependent manner: at high concentrations, it mimicked the AICAR effect on autophagy, whereas at low concentrations it stimulated autophagy through its cognate A1 receptor...
August 6, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29999247/combination-of-resveratrol-and-5-azacytydine-improves-osteogenesis-of-metabolic-syndrome-mesenchymal-stem-cells
#14
Krzysztof Marycz, Katarzyna Kornicka, Jennifer M Irwin-Houston, Christine Weiss
Endocrine disorders have become more and more frequently diagnosed in humans and animals. In horses, equine metabolic syndrome (EMS) is characterized by insulin resistance, hyperleptinemia, hyperinsulinemia, inflammation and usually by pathological obesity. Due to an increased inflammatory response in the adipose tissue, cytophysiological properties of adipose derived stem cells (ASC) have been impaired, which strongly limits their therapeutic potential. Excessive accumulation of reactive oxygen species, mitochondria deterioration and accelerated ageing of those cells affect their multipotency and restrict the effectiveness of the differentiation process...
July 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29995454/signals-in-stem-cell-differentiation-on-fluorapatite-modified-scaffolds
#15
T Guo, G Cao, Y Li, Z Zhang, J E Nör, B H Clarkson, J Liu
Previously, we reported that the fluorapatite (FA)-modified polycaprolactone (PCL) nanofiber could be an odontogenic/osteogenic inductive tissue-engineering scaffold by inducing stem cell differentiation and mineralization. The present study aimed to explore which of the signal pathways affected this differentiation and mineralization process. The Human Signal Transduction PathwayFinder RT2 Profiler PCR Array was used to analyze the involvement of potential signal transduction pathways during human dental pulp stem cell (DPSCs) osteogenic differentiation induced by FA-modified PCL nanofiber scaffolds...
July 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29990835/expression-kinetics-reveal-the-self-adaptive-role-of-%C3%AE-cells-during-the-progression-of-diabetes
#16
Shivani Srivastava, Harsh Pandey, Yamini Bhusan Tripathi
OBJECTIVE: To determine the histopathological and molecular changes in β-cells at different time intervals following streptozotocin (STZ)-induced diabetes. METHODS: STZ (65 mg/kg body weight) was given to overnight fasted rats that were sacrificed after 1, 3, and 10 days of injection. Changes in islet morphology and in the expression of various factors involved in β-cell proliferation, inflammation and apoptosis were analyzed. RESULTS: Superoxide dismutase (Sod) expression was completely reduced and that of NF-kB and iNOS were significantly increased, along with lymphocytic infiltration in the islets within 24 h of STZ injection...
July 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29988365/sex-differences-in-autophagy-contribute-to-female-vulnerability-in-alzheimer-s-disease
#17
REVIEW
Erin E Congdon
Alzheimer's disease (AD) is the most common form of dementia, with over 5. 4 million cases in the US alone (Alzheimer's Association, 2016). Clinically, AD is defined by the presence of plaques composed of Aβ and neurofibrillary pathology composed of the microtubule associated protein tau. Another key feature is the dysregulation of autophagy at key steps in the pathway. In AD, disrupted autophagy contributes to disease progression through the failure to clear pathological protein aggregates, insulin resistance, and its role in the synthesis of Aβ...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29986877/the-aging-heart
#18
REVIEW
Vanessa Obas, Ramachandran S Vasan
As the elderly segment of the world population increases, it is critical to understand the changes in cardiac structure and function during the normal aging process. In this review, we outline the key molecular pathways and cellular processes that underlie the phenotypic changes in the heart and vasculature that accompany aging. Reduced autophagy, increased mitochondrial oxidative stress, telomere attrition, altered signaling in insulin-like growth factor, growth differentiation factor 11, and 5'- AMP-activated protein kinase pathways are among the key molecular mechanisms underlying cardiac aging...
July 16, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29976399/resveratrol-protects-muscle-cells-against-palmitate-induced-cellular-senescence-and-insulin-resistance-through-ameliorating-autophagic-flux
#19
Yun-Ching Chang, Hung-Wen Liu, Yi-Tien Chen, Yun-An Chen, Yen-Ju Chen, Sue-Joan Chang
Skeletal muscle, a highly metabolic tissue, is particularly vulnerable to increased levels of saturated free fatty acids (FFAs). The role of autophagy in saturated FFAs-induced cellular senescence and insulin resistance in skeletal muscle remains unclear. Therefore, the present study was aimed to explore autophagic flux in cellular senescence and insulin resistance induced by palmitate in muscle cells, and whether resveratrol limited these responses. Our results showed that palmitate induced cellular senescence in both myoblasts and myotubes...
July 2018: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/29970188/chronic-restraint-stress-induces-hippocampal-memory-deficits-by-impairing-insulin-signaling
#20
Hanwoong Woo, Caroline Jeeyeon Hong, Seonghee Jung, Seongwon Choe, Seong-Woon Yu
Chronic stress is a psychologically significant factor that impairs learning and memory in the hippocampus. Insulin signaling is important for the development and cognitive function of the hippocampus. However, the relation between chronic stress and insulin signaling at the molecular level is poorly understood. Here, we show that chronic stress impairs insulin signaling in vitro and in vivo, and thereby induces deficits in hippocampal spatial working memory and neurobehavior. Corticosterone treatment of mouse hippocampal neurons in vitro caused neurotoxicity with an increase in the markers of autophagy but not apoptosis...
July 3, 2018: Molecular Brain
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