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Hypoxia Insulin

Xiang Song, Yan Zhang, Li Zhang, Wengang Song, Lixin Shi
Hypoxia-associated metabolic reprogramming modulates the biological functions of many immune and non-immune cells, and affects immune response types and intensities. Adenosine and indoleamine 2,3-dioxygenase (IDO) are known immunosuppressors, and adenosine is a hypoxia-associated product. We investigated the impact of hypoxia on IDO production in dendritic cells (DCs). We found that hypoxia (1% O2 ) enhances IDO production in DCs, and this increase was dependent on the adenosine A3 receptor (A3R), but not A2aR or A2bR...
February 20, 2018: Oncotarget
Charles Cai, Taimur Ahmad, Gloria B Valencia, Jacob V Aranda, Jiliu Xu, Kay D Beharry
OBJECTIVES: Extremely low gestational age neonates with chronic lung disease requiring oxygen therapy frequently experience fluctuations in arterial oxygen saturation or intermittent hypoxia (IH). These infants are at risk for multi-organ developmental delay, reduced growth, and short stature. The growth hormone (GH)/insulin-like growth factor-I (IGF-1) system, an important hormonal regulator of lipid and carbohydrate metabolism, promotes neonatal growth and development. We tested the hypothesis that increasing episodes of IH delay neonatal growth by influencing the GH/IGF-I axis...
March 8, 2018: Growth Hormone & IGF Research
Asim Badar, Zarina Arif, Khursheed Alam
Carbamylation (or carbamoylation) is a non-enzymatic modification of biomolecules mediated by cyanate, a dissociation product of urea. Proteins are more sensitive to carbamylation. Two major sites of carbamylation reaction are: Nα -amino moiety of a protein N-terminus and the Nɛ -amino moiety of proteins' lysine residues. In kidney diseases, urea accumulates and the burden of carbamylation increases. This may lead to alteration in the structure and function of many important proteins relevant in maintenance of homeostasis...
March 15, 2018: IUBMB Life
Yuxian Yang, Xiaorong Fan, Jianying Tao, Ting Xu, Yingying Zhang, Wenna Zhang, Lingjun Li, Xiang Li, Hongmei Ding, Miao Sun, Qinqin Gao, Zhice Xu
Prenatal hypoxia causes intrauterine growth retardation. It is unclear whether/how hypoxia affects the bone in fetal and offspring life. This study showed that prenatal hypoxia retarded fetal skeletal growth in rats, inhibited extracellular matrix (ECM) synthesis and down-regulated of insulin-like growth factor 1 (IGF1) signaling in fetal growth plate chondrocytes in vivo and in vitro. In addition, ovariectomized (OVX) was used for study of postmenopausal osteoporosis. Compared with the control, OVX offspring in prenatal hypoxic group showed an enhanced osteoporosis in the femurs, associated with reduced proteoglycan and IGF1 signaling...
March 7, 2018: Reproductive Toxicology
Ni Yang, Liuzhong Wu, Ying Zhao, Ning Zou, Chunfeng Liu
It is generally accepted that insulin exerts an antiapoptotic effect against ischemia/reperfusion through the activation of PI3K/Akt/mTOR pathway. MicroRNAs involve in multiple cardiac pathophysiological processes, including ischemia/reperfusion-induced cardiac injury. However, the regulation of microRNAs in the cardioprotective effect of insulin is rarely discussed. In this study, using a cell model of ischemia through culturing H9C2 cardiac myocytes in serum-free medium with hypoxia, we demonstrated that pretreatment with insulin significantly inhibited cell apoptosis and downregulated microRNA-320 (miR-320) expression...
March 9, 2018: Cell Biochemistry and Function
F Louwen, A Ritter, N N Kreis, J Yuan
Obesity is associated with a variety of disorders including cardiovascular diseases, diabetes mellitus and cancer. Obesity changes the composition and structure of adipose tissue, linked to pro-inflammatory environment, endocrine/metabolic dysfunction, insulin resistance and oxidative stress. Adipose-derived mesenchymal stem cells (ASCs) have multiple functions like cell renewal, spontaneous repair and homeostasis in adipose tissue. In this review article, we have summarized the recent data highlighting that ASCs in obesity are defective in various functionalities and properties including differentiation, angiogenesis, motility, multipotent state, metabolism and immunomodulation...
March 8, 2018: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Veronica Moreno-Viedma, Matteo Tardelli, Maximilian Zeyda, Maria Sibilia, J Deborah Burks, M Thomas Stulnig
OBJECTIVE: Osteopontin (OPN, Spp1) is a protein upregulated in white adipose tissue (WAT) of obese subjects. Deletion of OPN protects mice from high-fat diet-induced WAT inflammation and insulin resistance. However, the alterations mediated by loss of OPN in WAT before the obesogenic challenge have not yet been investigated. Therefore, we hypothesised that the lack of OPN might enhance the pro-adipogenic micro environment before obesity driven inflammation. METHODS: OPN deficiency was tested in visceral (V) and subcutaneous (SC) WAT from WT and Spp1-/- female mice...
March 6, 2018: Obesity Research & Clinical Practice
Christine Brütting, Harini Narasimhan, Frank Hoffmann, Malte E Kornhuber, Martin S Staege, Alexander Emmer
Human endogenous retroviruses (ERVs) have been found to be associated with different diseases, e.g., multiple sclerosis (MS). Most human ERVs integrated in our genome are not competent to replicate and these sequences are presumably silent. However, transcription of human ERVs can be reactivated, e.g., by hypoxia. Interestingly, MS has been linked to hypoxia since decades. As some patterns of demyelination are similar to white matter ischemia, hypoxic damage is discussed. Therefore, we are interested in the association between hypoxia and ERVs...
2018: Frontiers in Microbiology
Qun Tang, Hua Wu, Jiushi Lei, Chun Yi, Wenfeng Xu, Wenqu Lan, Fang Yang, Chunyan Liu
Adipose stem cell (ASC) transplantation is a promising therapeutic strategy for diabetic renal fibrosis. Hypoxia-inducible factor 1α (HIF1α) is a negative regulatory factor of mitochondrial function. In the current study, we aimed to explore if HIF1α deletion protects against hyperglycemia-induced ASC damage and enhances the therapeutic efficiency of ASCs in diabetic renal fibrosis. Our data indicated that HIF1α was upregulated in ASCs in response to high glucose stimulation. Higher HIF1α expression was associated with ASC apoptosis and proliferation arrest...
March 6, 2018: In Vitro Cellular & Developmental Biology. Animal
Soon-Hee Kim, Hee-Sook Park, Moon Ju Hong, Haeng Jeon Hur, Dae Young Kwon, Myung-Sunny Kim
SCOPE: This study investigated the effects of caffeic acid phenethyl ester (CAPE), a bioactive component of honeybee hives, on the prevention and treatment of metabolic syndrome (MetS) by comparing the efficacy of CAPE intake at the beginning of obesity and after obesity. The functional mechanism of CAPE was also investigated. METHODS AND RESULTS: C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% CAPE (HFD+C) for 12 weeks (HFD+C(Pre) group) or received HFD+C for 6 weeks after consuming the HFD for 6 weeks (HFD+C(Post) group)...
March 5, 2018: Molecular Nutrition & Food Research
Simona Ioja, Srikanth Singamsetty, Catherine Corey, Lanping Guo, Faraaz Shah, Michael J Jurczak, Bryan J McVerry, Sruti Shiva, Christopher P O'Donnell
Although acute exposure to hypoxia can disrupt metabolism, longer-term exposure may normalize glucose homeostasis or even improve glucose disposal in the presence of obesity. We examined the effects of two-week exposure to room air (Air), continuous 10% oxygen (C10%), and 12 hr nocturnal periods of 10% oxygen (N10%) on glucose disposal, insulin responsiveness, and mitochondrial function in lean and obese C57BL/6J mice. Both C10% and N10% improved glucose disposal relative to Air in lean and obese mice without evidence of an increase in insulin responsiveness; however, only the metabolic improvements with N10% exposure occurred in the absence of confounding effects of weight loss...
2018: Oxidative Medicine and Cellular Longevity
Rajesh Guruswamy Damodaran, Patrick Vermette
Diabetes Mellitus involves the loss of function and/or absolute numbers of insulin-producing β-cells in pancreatic islets. Islet transplantation is currently being investigated as a potential cure, and advances in tissue engineering methods can be used to improve pancreatic islets survival and functionality. Transplanted islets experience anoikis, hypoxia and inflammation-mediated immune response, leading to early damage and subsequent failure of the graft. Recent development in tissue engineering enables the use of decellularized organs as scaffolds for cell therapies...
March 2, 2018: Journal of Tissue Engineering and Regenerative Medicine
Sílvia Rocha-Rodrigues, Inês O Gonçalves, Jorge Beleza, António Ascensão, José Magalhães
The dysregulation of adipokine secretion owing to adiposopathy can contribute to the pathogenesis of obesity-related disorders. Being that exercise is an advised strategy against obesity-induced adiposopathy, we aimed to analyze the role of physical exercise as a preventive and therapeutic strategy against high-fat diet (HFD)-induced adipokine and ghrelin alterations. Rats were pair-fed the Lieber De Carli standard diet (S, 35 Kcal% fat) or HFD (71 Kcal% fat) over 17 weeks. Animals were assigned into four groups as follows: standard diet sedentary (SS), standard diet voluntary physical activity (SVPA), high-fat diet sedentary (HS), and high-fat diet voluntary physical activity (HVPA)...
February 24, 2018: Journal of Physiology and Biochemistry
Luís Crisóstomo, Marco G Alves, Agostina Gorga, Mário Sousa, María F Riera, María N Galardo, Silvina B Meroni, Pedro F Oliveira
Sertoli cells play a central role in spermatogenesis. They maintain the blood-testis barrier, an essential feature of seminiferous tubules which creates the proper environment for the occurrence of the spermatogenesis. However, this confinement renders germ cells almost exclusively dependent on Sertoli cells' nursing function and support. Throughout spermatogenesis, differentiating sperm cells become more specialized, and their biochemical machinery is insufficient to meet their metabolic demands. Although the needs are not the same at all differentiation stages, Sertoli cells are able to satisfy their needs...
2018: Methods in Molecular Biology
Yinglan Peng, Ke Hu
The present study investigated the effect of garlic (G) on serum, liver, renal and cerebral parameters of rats with chronic intermittent hypoxia (CIH) combined with diabetes mellitus (DM). A total of 32 rats were divided into eight groups, with 4 rats/group. A total of three models were established, including CIH, DM and CIH‑DM, and an additional healthy control (C) group. Rats in C‑G, CIH‑G, DM‑G and CIH‑DM‑G groups were injected with a G extract daily. Serum, liver, renal and cerebral parameters were detected...
February 7, 2018: Molecular Medicine Reports
Naomi Dirckx, Robert J Tower, Evi M Mercken, Roman Vangoitsenhoven, Caroline Moreau-Triby, Tom Breugelmans, Elena Nefyodova, Ruben Cardoen, Chantal Mathieu, Bart Van der Schueren, Cyrille B Confavreux, Thomas L Clemens, Christa Maes
The skeleton has emerged as an important regulator of systemic glucose homeostasis, with osteocalcin and insulin representing prime mediators of the interplay between bone and energy metabolism. However, genetic evidence indicates that osteoblasts can influence global energy metabolism through additional, as yet unknown, mechanisms. Here, we report that constitutive or postnatally induced deletion of the hypoxia signaling pathway component von Hippel-Lindau (VHL) in skeletal osteolineage cells of mice led to high bone mass as well as hypoglycemia and increased glucose tolerance, not accounted for by osteocalcin or insulin...
February 12, 2018: Journal of Clinical Investigation
Jordan Rowlands, Vinicius Cruzat, Rodrigo Carlessi, Philip Newsholme
Pharmacological long lasting Glucagon-like peptide-1 (GLP-1) analogues, such as Exendin-4, have become widely used diabetes therapies. Chronic GLP-1R stimulation has been linked to β-cell protection and these pro-survival actions of GLP-1 are dependent on the activation of the mammalian target of rapamycin (mTOR) leading to accumulation of Hypoxia inducible factor 1 alpha (HIF-1α). Recent studies from our lab indicate that prolonged GLP-1R stimulation promotes metabolic reprograming of β-cells towards a highly glycolytic phenotype and activation of the mTOR/HIF-1α pathway was required for this action...
February 2018: Peptides
Katarzyna Karwasik-Kajszczarek, Iwona Chmiel-Perzyńska, Jacek Marcin Robak, Aleksandra Billewicz-Kraczkowska, Agnieszka Pedrycz, Agata Smoleń, Janusz Jacek Kraczkowski
OBJECTIVES: The aim of the study is to determine the impact of the experimental diabetes and the chronic hypoxia on pregnancy development and rat fetal body weight. MATERIAL AND METHODS: The experiment was performed on female Wistar rats. Animals were divided into the experimen-tal groups. I - Controls, II - Untreated diabetes, III - Insulin-treated diabetes, IV - No diabetes with chronic hypoxia, V - Untreated diabetes and chronic hypoxia, VI - Insulin- treated diabetes and chronic hypoxia...
2018: Ginekologia Polska
M Varela-Guruceaga, F I Milagro, J A Martínez, C de Miguel
Obesity is characterized by hypertrophy and hyperplasia of adipose tissue, which have been related to the development of hypoxia and insulin resistance. On the other hand, caveolin-1 (Cav-1), one of the main proteins of caveolae, promotes insulin receptor (IR) phosphorylation and the subsequent activation of insulin signaling. In this work we investigated the effect of hypoxia on Cav-1 regulation and the status of insulin signaling in 3T3-L1 adipocytes. Our results showed that hypoxia inhibited adipogenesis and insulin signaling in adipocytes...
January 30, 2018: Molecular and Cellular Endocrinology
Hiroyasu Kamei, Yosuke Yoneyama, Fumihiko Hakuno, Rie Sawada, Toshiaki Shimizu, Cunming Duan, Shin-Ichiro Takahashi
Most animals display retarded growth in adverse conditions; however, upon the removal of unfavorable factors, they often show quick growth restoration, which is known as "catch-up" growth. In zebrafish embryos, hypoxia causes growth arrest but subsequent reoxygenation induces the catch-up growth. Here we report the role of Irs1-mediated insulin/insulin-like growth factor signaling (IIS) and the involvement of stem cells in catch-up growth in reoxygenated zebrafish embryos. Disturbed irs1 expression attenuated IIS resulting in greater growth inhibition in catch-up growth than in normal growth, and forced IIS-activation restored the catch-up growth...
January 30, 2018: Endocrinology
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