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Hypoxia Insulin

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https://www.readbyqxmd.com/read/28431667/the-potential-and-pitfalls-of-glp-1-receptor-agonists-for-renal-protection-in-type-2-diabetes
#1
Merlin C Thomas
Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) offer substantial benefits for the management of glucose levels in type 2 diabetes. In addition, recent data from clinical trials have demonstrated that treatment with Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) are also able to reduce new onset macroalbuminuria. These benefits may be consistent with the known effects of GLP-1 RA on traditional risk factors for progressive kidney disease including glucose lowering, blood pressure lowering, reduced insulin levels and weight reduction...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28426078/an-intravascular-bioartificial-pancreas-device-ibap-with-silicon-nanopore-membranes-snm-for-islet-encapsulation-under-convective-mass-transport
#2
Shang Song, Charles Blaha, Willieford Moses, Jaehyun Park, Nathan Wright, Joey Groszek, William Fissell, Shant Vartanian, Andrew M Posselt, Shuvo Roy
Diffusion-based bioartificial pancreas (BAP) devices are limited by poor islet viability and functionality due to inadequate mass transfer resulting in islet hypoxia and delayed glucose-insulin kinetics. While intravascular ultrafiltration-based BAP devices possess enhanced glucose-insulin kinetics, the polymer membranes used in these devices provide inadequate ultrafiltrate flow rates and result in excessive thrombosis. Here, we report the silicon nanopore membrane (SNM), which exhibits a greater hydraulic permeability and a superior pore size selectivity compared to polymer membranes for use in BAP applications...
April 20, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28424360/intermittent-hypoxia-in-obstructive-sleep-apnoea-mediates-insulin-resistance-through-adipose-tissue-inflammation
#3
Aoife M Murphy, Amandine Thomas, Sophie J Crinion, Brian D Kent, Murtaza M Tambuwala, Aurelie Fabre, Jean-Louis Pepin, Helen M Roche, Claire Arnaud, Silke Ryan
Obstructive sleep apnoea (OSA) is increasingly associated with insulin resistance. The underlying pathophysiology remains unclear but intermittent hypoxia (IH)-mediated inflammation and subsequent dysfunction of the adipose tissue has been hypothesised to play a key role.We tested this hypothesis employing a comprehensive translational approach using a murine IH model of lean and diet-induced obese mice, an innovative IH system for cell cultures and a tightly controlled patient cohort.IH led to the development of insulin resistance in mice, corrected for the degree of obesity, and reduced insulin-mediated glucose uptake in 3T3-L1 adipocytes, associated with inhibition of the insulin-signalling pathway and downregulation of insulin-receptor substrate-1 mRNA...
April 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28420864/insulin-growth-factor-1-protects-neural-stem-cells-against-apoptosis-induced-by-hypoxia-through-akt-mitogen-activated-protein-kinase-extracellular-signal-regulated-kinase-akt-mapk-erk-pathway-in-hypoxia-ishchemic-encephalopathy
#4
Bing Zhao, Zebao Zheng
BACKGROUND Insulin growth factor 1 (IGF-1) is reported to modulate cell growth and acts as potential therapy for traumatic brain injury. This study was designed to investigate the effect of IGF-1 on hypoxia-induced apoptosis in neural stem cells (NSCs). MATERIAL AND METHODS A hypoxia model was constructed using NSCs separated from the hippocampus of rat. NSCs were divided into four groups: cells under normoxic conditions that acted as controls (C group), cells under hypoxia (H group), cells under hypoxia with IGF-1 (HI group), and cells under hypoxia with IGF-1 as well as picropodophyllin (PPP), which acts as an inhibitor of the IGF-1 receptor (HIP group)...
April 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28410399/altered-glucose-metabolism-and-hypoxic-response-in-alloxan-induced-diabetic-atherosclerosis-in-rabbits
#5
Yunosuke Matsuura, Atsushi Yamashita, Yan Zhao, Takashi Iwakiri, Kazuaki Yamasaki, Chihiro Sugita, Chihiro Koshimoto, Kazuo Kitamura, Keiichi Kawai, Nagara Tamaki, Songji Zhao, Yuji Kuge, Yujiro Asada
Diabetes mellitus accelerates atherosclerosis that causes most cardiovascular events. Several metabolic pathways are considered to contribute to the development of atherosclerosis, but comprehensive metabolic alterations to atherosclerotic arterial cells remain unknown. The present study investigated metabolic changes and their relationship to vascular histopathological changes in the atherosclerotic arteries of rabbits with alloxan-induced diabetes. Diabetic atherosclerosis was induced in rabbit ilio-femoral arteries by injecting alloxan (100 mg/kg), injuring the arteries using a balloon, and feeding with a 0...
2017: PloS One
https://www.readbyqxmd.com/read/28394654/inhibiting-igf-1r-attenuates-cell-proliferation-and-vegf-production-in-igf-1r-over-expressing-egfr-mutant-non-small-cell-lung-cancer-cells
#6
Chang Dong Yeo, Young Ae Kim, Hwa Young Lee, Jin Woo Kim, Sang Haak Lee, Seung Joon Kim, Soon Seog Kwon, Yong Hyun Kim, Seok Chan Kim
PURPOSE: The aim of the present study was to demonstrate the role of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitors (TKIs) in IGF-1R expressed epidermal growth factor receptor (EGFR) mutant cells. MATERIALS AND METHODS: Human lung adenocarcinoma PC9, HCC827, and H1975 cells were exposed to a combination of IGF-1, gefitinib, or linsitinib. Cell viability was assessed by the MTT assay. The expression of EGFR, IGF-1R, AKT, extracellular regulated kinases 1 and 2 (ERK1/2), cleaved poly ADP ribose polymerase (PARP), cleaved caspase 3, and hypoxia-inducible factor (HIF)-1α were measured by Western blot...
February 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28394459/ergogenic-properties-of-metformin-in-simulated-high-altitude
#7
Rebecca L Scalzo, Hunter L Paris, Scott E Binns, Janelle L Davis, Joseph W Beals, Christopher L Melby, Gary J Luckasen, Matthew S Hickey, Benjamin F Miller, Karyn L Hamilton, Christopher Bell
Metformin augments glucose/glycogen regulation and may acutely promote fatigue resistance during high-intensity exercise. In hypobaric environments, such as high altitude, the important contribution of carbohydrates to physiological function is accentuated as glucose/glycogen dependence is increased. Because hypoxia/hypobaria decreases insulin sensitivity, replenishing skeletal muscle glycogen in high altitude becomes challenging and subsequent physical performance may be compromised. We hypothesized that in conditions where glycogen repletion was critical to physical outcomes, metformin would attenuate hypoxia-mediated decrements in exercise performance...
April 10, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28382782/fatty-acid-binding-protein-4-regulates-fatty-infiltration-after-rotator-cuff-tear-by-hypoxia-inducible-factor-1-in-mice
#8
Yong-Soo Lee, Ja-Yeon Kim, Kyung-Soo Oh, Seok Won Chung
BACKGROUND: Fatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined...
April 5, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28364040/hypoxia-reduces-hnf4%C3%AE-mody1-protein-expression-in-pancreatic-%C3%AE-cells-by-activating-amp-activated-protein-kinase
#9
Yoshifumi Sato, Tomonori Tsuyama, Chinami Sato, Md Fazlul Karim, Tatsuya Yoshizawa, Masahiro Inoue, Kazuya Yamagata
Hypoxia plays a role in the deterioration of β-cell function. Hepatocyte nuclear factor 4α (HNF4α) has an important role in pancreatic β-cells, and mutations of the human HNF4A gene cause a type of maturity-onset diabetes of the young (MODY1). However, it remains unclear whether hypoxia affects the expression of HNF4α in β-cells. Here, we report that hypoxia reduces HNF4α protein expression in β-cells. Hypoxia-inducible factor (HIF) was not involved in the down-regulation of HNF4α under hypoxic conditions...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28359241/obesity-and-cancer-biological-links-and-treatment-implications
#10
Alessandro Ottaiano, Chiara De Divitiis, Monica Capozzi, Antonio Avallone, Carmen Pisano, Sandro Pignata, Salvatore Tafuto
Obesity is an epidemic disease and correlates with cardiovascular diseases increasing the overall mortality. However, it has been recently demonstrated that cancer is an unexpected consequence of obesity. In most of the studies it is evaluated with body mass index (BMI): high BMI increases cancer risk and reduces survival of many solid tumors. The main biologic and clinic topics regarding obese cancer patients are here presented and discussed. Hyperinsulinemia and Insulin-like Growth Factors (IGFs) are among the most important links between cancer and obesity...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28329220/prolonged-exposures-to-intermittent-hypoxia-promote-visceral-white-adipose-tissue-inflammation-in-a-murine-model-of-severe-sleep-apnea-effect-of-normoxic-recovery
#11
Alex Gileles-Hillel, Isaac Almendros, Abdelnaby Khalyfa, Recep Nigdelioglu, Zhuanhong Qiao, Robert B Hamanaka, Gökhan M Mutlu, Mahzad Akbarpour, David Gozal
Study Objective: Increased visceral white adipose tissue (vWAT) mass results in infiltration of inflammatory macrophages that drive inflammation and insulin resistance. Patients with obstructive sleep apnea (OSA) suffer from increased prevalence of obesity, insulin resistance, and metabolic syndrome. Murine models of intermittent hypoxia (IH) mimicking moderate-severe OSA manifest insulin resistance following short-term IH. We examined in mice the effect of long-term IH on the inflammatory cellular changes within vWAT and the potential effect of normoxic recovery (IH-R)...
March 1, 2017: Sleep
https://www.readbyqxmd.com/read/28315973/stem-cell-factor-kit-signal-insufficiency-contributes-to-hypoxia-induced-intestinal-motility-dysfunctions-in-neonatal-mice
#12
Hong Ren, Juan Han, Zhifang Li, Zhiyong Xiong
BACKGROUND: Gastrointestinal (GI) motility disorders represent a group of problems that more constantly encountered in preterm infants. However, whether hypoxia exposure contributes to the GI dysfunctions is still unclear. METHODS: Newborn mice were exposed to hypoxia (10%) from P1 to P7. Intestinal motilities were examined by a strain gauge transducer. The proliferation of ICCs was detected by using immunostaining for BrdU, Ki67, Kit, Ano1, and insulin-like growth factor 1 receptor (IGF-1R+)...
May 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28302721/involvement-of-notch1-signaling-in-malignant-progression-of-a549-cells-subjected-to-prolonged-cadmium-exposure
#13
Kota Fujiki, Hisako Inamura, Takamitsu Miyayama, Masato Matsuoka
Cadmium exposure is known to increase lung cancer risk, but the underlying molecular mechanisms in cadmium-stimulated progression of malignancy are unclear. Here, we examined the effects of prolonged cadmium exposure on the malignant progression of A549 human lung adenocarcinoma cells and the roles of Notch1, hypoxia-inducible factor 1α (HIF-α), and insulin-like growth factor 1 receptor (IGF-1R)/Akt/extracellular signal-regulated kinase (ERK)/p70 S6 kinase 1 (S6K1) signaling pathways. Exposing A549 cells to 10 or 20 μM cadmium chloride (CdCl2) for 9-15 weeks induced a high proliferative potential, the epithelial-mesenchymal transition (EMT), stress fiber formation, high cell motility, and resistance to anti-tumor drugs...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28295307/high-expression-of-insulin-receptor-on-tumor-associated-blood-vessels-in-invasive-bladder-cancer-predicts-poor-overall-and-progression-free-survival
#14
Filip Roudnicky, Lothar C Dieterich, Cedric Poyet, Lorenz Buser, Peter Wild, Dave Tang, Peter Camenzind, Chien Hsien Ho, Vivianne I Otto, Michael Detmar
Bladder cancer is a frequently recurring disease with a very poor prognosis when progressed to invasive stages, and tumor-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumor-associated BECs greatly upregulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival...
March 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28291256/exercise-rescues-obese-mothers-insulin-sensitivity-placental-hypoxia-and-male-offspring-insulin-sensitivity
#15
Denise S Fernandez-Twinn, Geraldine Gascoin, Barbara Musial, Sarah Carr, Daniella Duque-Guimaraes, Heather L Blackmore, Maria Z Alfaradhi, Elena Loche, Amanda N Sferruzzi-Perri, Abigail L Fowden, Susan E Ozanne
The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28290159/the-unexplored-crossroads-of-the-female-athlete-triad-and-iron-deficiency-a-narrative-review
#16
REVIEW
Dylan L Petkus, Laura E Murray-Kolb, Mary Jane De Souza
Despite the severity and prevalence of iron deficiency in exercising women, few published reports have explored how iron deficiency interacts with another prevalent and severe condition in exercising women: the 'female athlete triad.' This review aims to describe how iron deficiency may interact with each component of the female athlete triad, that is, energy status, reproductive function, and bone health. The effects of iron deficiency on energy status are discussed in regards to thyroid function, metabolic fuel availability, eating behaviors, and energy expenditure...
March 13, 2017: Sports Medicine
https://www.readbyqxmd.com/read/28263224/acute-ischemia-induced-by-high-density-culture-increases-cytokine-expression-and-diminishes-the-function-and-viability-of-highly-purified-human-islets-of-langerhans
#17
Kate E Smith, Amy C Kelly, Catherine G Min, Craig S Weber, Fiona M McCarthy, Leah V Steyn, Vasudeo Badarinarayana, J Brett Stanton, Jennifer P Kitzmann, Peter Strop, Angelika C Gruessner, Ronald M Lynch, Sean W Limesand, Klearchos K Papas
BACKGROUND: Encapsulation devices have the potential to enable cell based insulin replacement therapies (such as human islet or stem cell derived β cell transplantation) without immunosuppression. However, reasonably sized encapsulation devices promote ischemia due to high β cell densities creating prohibitively large diffusional distances for nutrients. It is hypothesized that even acute ischemic exposure will compromise the therapeutic potential of cell based insulin replacement. In this study, the acute effects of high-density ischemia were investigated in human islets to develop a detailed profile of early ischemia induced changes and targets for intervention...
March 3, 2017: Transplantation
https://www.readbyqxmd.com/read/28261091/ginsenoside-rg5-inhibits-succinate-associated-lipolysis-in-adipose-tissue-and-prevents-muscle-insulin-resistance
#18
Na Xiao, Le-Le Yang, Yi-Lin Yang, Li-Wei Liu, Jia Li, Baolin Liu, Kang Liu, Lian-Wen Qi, Ping Li
Endoplasmic reticulum (ER) stress, inflammation, and lipolysis occur simultaneously in adipose dysfunction and contribute to insulin resistance. This study was designed to investigate whether ginsenoside Rg5 could ameliorate adipose dysfunction and prevent muscle insulin resistance. Short-term high-fat diet (HFD) feeding induced hypoxia with ER stress in adipose tissue, leading to succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activity. Rg5 treatment reduced cellular energy charge, suppressed ER stress and then prevented succinate accumulation in adipose tissue...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28260056/insulin-like-growth-factor-1-receptor-mediated-cell-survival-in-hypoxia-depends-on-the-promotion-of-autophagy-via-suppression-of-the-pi3k-akt-mtor-signaling-pathway
#19
Qi Liu, Jing-Zhi Guan, Yong Sun, Ziyu Le, Ping Zhang, Dong Yu, Yong Liu
Hypoxia is widely accepted as a fundamental biological phenomenon, which is strongly associated with tissue damage and cell viability under stress conditions. Insulin-like growth factor‑1 (IGF‑1) is known to protect tissues from multiple types of damage, and protect cells from apoptosis. Hypoxia is a regulatory factor of the IGF system, however the role of the IGF-1 receptor (IGF‑1R) in hypoxia‑induced apoptosis remains unclear. The present study investigated the potential mechanisms associated with IGF‑1R‑associated apoptosis under hypoxic conditions...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28255159/high-intensity-aerobic-exercise-training-improves-chronic-intermittent-hypoxia-induced-insulin-resistance-without-basal-autophagy-modulation
#20
Marion Pauly, Allan Assense, Aurélie Rondon, Amandine Thomas, Hervé Dubouchaud, Damien Freyssenet, Henri Benoit, Josiane Castells, Patrice Flore
Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21-5% FiO2, 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT)...
March 3, 2017: Scientific Reports
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