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Hypoxia and diabetes

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https://www.readbyqxmd.com/read/28931763/reversible-retinal-vessel-closure-from-vegf-induced-leukocyte-plugging
#1
Yuanyuan Liu, Jikui Shen, Seth D Fortmann, Jiangxia Wang, Dietmar Vestweber, Peter A Campochiaro
Clinical trials in patients with macular edema due to diabetic retinopathy or retinal vein occlusion (RVO) have shown that suppression of VEGF not only improves macular edema, but also reopens closed retinal vessels, prevents progression of vessel closure, and improves retinopathy. In this study, we show the molecular basis for those clinical observations. Increased retinal levels of VEGF in mice cause plugging of retinal vessels with leukocytes, vessel closure, and hypoxia. Suppression of VEGF reduces leukocyte plugging, causing reperfusion of closed vessels...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28926865/effects-of-hypoxia-during-continuous-and-intermittent-exercise-on-glycaemic-control-and-selected-markers-of-vascular-function-in-type-1-diabetes
#2
Barbara Hall, Aleksandra Zebrowska, Tomasz Kaminski, Arkadiusz Stanula, Anna Robins
Objectives The aim of the study was to assess the effect of continuous and intermittent exercise in hypoxia on glycaemic control and selected markers of vascular function in patients with Type 1 diabetes (T1D). Methods 12 patients suffering from T1D for 12.1±6.0 years and 12 healthy adults performed: continuous exercise (ExC) and intermittent exercise (ExInt) in normoxia and hypoxia (FiO₂=15.1%). Glycaemia and proangiogenic factors concentrations were measured at rest and immediately after exercise. Results T1D patients' glycaemia decreased in response to ExC (p<0...
September 19, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28923778/links-between-lower-urinary-tract-symptoms-intermittent-hypoxia-and-diabetes-causes-or-cures
#3
REVIEW
Lisa L Abler, Chad M Vezina
Bothersome lower urinary tract symptoms (LUTS) manifest as urinary frequency, urgency, incontinence and incomplete bladder emptying. Existing treatments ameliorate but do not eliminate most symptoms, leading to financial and personal burdens attributable to sustained medical therapies that may last a lifetime. The purpose of this review is to highlight evidence of causal associations between LUTS and several common comorbidities, including intermittent hypoxia (IH) concomitant with obstructive sleep apnea (OSA), obesity, metabolic syndrome and type 2 diabetes...
September 15, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28923269/dpp-4-inhibition-protects-human-umbilical-vein-endothelial-cells-from-hypoxia-induced-vascular-barrier-impairment
#4
Naoko Hashimoto, Kento Ikuma, Yui Konno, Masanori Hirose, Hiroyuki Tadokoro, Hiroshi Hasegawa, Yoshio Kobayashi, Hiroyuki Takano
Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor...
August 26, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28916390/il-33-receptor-st2-deficiency-attenuates-renal-ischaemia-reperfusion-injury-in-euglycaemic-but-not-streptozotocin-induced-hyperglycaemic-mice
#5
M Sehnine, M Ferhat, S Sena, J M Gombert, J M Goujon, A Thierry, G Touchard, T Hauet, A Herbelin, S Hadjadj
AIM: Kidney hypoxia can predispose to the development of acute and chronic renal failure in diabetes. Ischaemia-reperfusion injury (IRI) causes inflammation, and diabetes is known to exacerbate this inflammatory response in the kidney, whereas alarmin IL-33 could act as an innate immune mediator during kidney IRI. Thus, the present study examined the impact of genetic IL-33 receptor ST2 deficiency (ST2-/-) on renal IRI in euglycaemic and hyperglycaemic mice. METHODS: Hyperglycaemia was induced with streptozotocin (STZ) in adult male C57BL/6JRj wild-type (WT) mice and ST2-/- mice...
September 12, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28900259/selective-tubular-activation-of-hypoxia-inducible-factor-2%C3%AE-has-dual-effects-on-renal-fibrosis
#6
Kyoung Hye Kong, Hyung Jung Oh, Beom Jin Lim, Minsuk Kim, Ki-Hwan Han, Youn-Hee Choi, Kihwan Kwon, Bo Young Nam, Kyoung Sook Park, Jung Tak Park, Seung Hyeok Han, Tae-Hyun Yoo, Shina Lee, Seung-Jung Kim, Duk-Hee Kang, Kyu Bok Choi, Vera Eremina, Susan E Quaggin, Dong-Ryeol Ryu, Shin-Wook Kang
Hypoxia-inducible factor (HIF) is a key transcriptional factor in the response to hypoxia. Although the effect of HIF activation in chronic kidney disease (CKD) has been widely evaluated, the results have been inconsistent until now. This study aimed to investigate the effects of HIF-2α activation on renal fibrosis according to the activation timing in inducible tubule-specific transgenic mice with non-diabetic CKD. HIF-2α activation in renal tubular cells upregulated mRNA and protein expressions of fibronectin and type 1 collagen associated with the activation of p38 mitogen-activated protein kinase...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898528/post-transplant-oxygen-inhalation-improves-the-outcome-of-subcutaneous-islet-transplantation-a-promising-clinical-alternative-to-the-conventional-intrahepatic-site
#7
H Komatsu, J Rawson, A Barriga, N Gonzalez, D Mendez, J Li, K Omori, F Kandeel, Y Mullen
Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose-bFGF...
September 12, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28888981/hypoxia-in-3t3-l1-adipocytes-suppresses-adiponectin-expression-via-the-perk-and-ire1-unfolded-protein-response
#8
Qian Guo, Sanli Jin, Hailong Hu, Ying Zhou, Yuheng Yan, He Zong, Yu Wang, Hongjuan He, Yuri Oh, Chuanpeng Liu, Ning Gu
Adiponectin, an adipocytokine produced by adipocytes, functions as an anti-inflammatory and anti-apoptotic substance, while also enhancing insulin sensitivity. Patients or model animals with obesity or diabetes typically present attenuated expression of adiponectin. Moreover, obesity and diabetes are often accompanied with hypoxia in adipose tissue, which may result in endoplasmic reticulum (ER) stress as well as low expression of adiponectin. The purpose of this study was to investigate the specific role of the unfolded protein response (UPR) involved in the low expression of adiponectin induced by hypoxia...
September 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28867579/socs2-exacerbates-myocardial-injury-induced-by-ischemia-reperfusion-in-diabetic-mice-and-h9c2-cells-through-inhibiting-the-jak-stat-igf-1-pathway
#9
Mengting Sheng, Zirui Huang, Liming Pan, Min Yu, Cai Yi, Lin Teng, Ling He, Chen Gu, Chunli Xu, Junming Li
AIMS: This study aimed to investigate potential candidates and molecular mechanisms of myocardial ischemia/reperfusion (I/R) injury (MIRI) in type 2 diabetes mellitus. MAIN METHODS: Type 2 diabetic and myocardial I/R mouse models were established with a high fat-diet (HFD) for 24weeks and subjecting to global ischemia/reperfusion for 1h/3h, respectively. Microarray analysis was applied to screen differentially expressed genes (DEGs) in the hearts of these mice. Moreover, H9c2 cells were treated with high glucose (HG) and/or hypoxia and reoxygenation (H/R)...
August 31, 2017: Life Sciences
https://www.readbyqxmd.com/read/28865439/apln-creert-mt-mg-reporter-mice-as-a-tool-for-sprouting-angiogenesis-study
#10
Jingjiang Pi, Yu Cheng, Huimin Sun, Xiaoli Chen, Tao Zhuang, Jie Liu, Yixi Li, Huan Chang, Lin Zhang, YuZhen Zhang, Ting Tao
BACKGROUND: Angiogenesis is defined as a new blood vessel sprouting from pre-existing vessels, and the sprouting angiogenesis is the start phase of angiogenesis, which is critical for both physiological and pathological processes, such as embryonic development, organ growth, wound healing, tumor growth, diabetic retinopathy and age-related macular degeneration. Better understanding of the mechanisms of sprout angiogenesis will provide a rationale for the treatments of these angiogenesis related diseases...
September 2, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28851567/association-of-down-regulation-of-calcitonin-gene-related-peptide-and-substance-p-with-increase-of-myocardial-vulnerability-in-diabetic-neuropathic-rats
#11
Tu-Ping Li, Zheng Guo, Chao-Jie Liu, Tao Sun, Lu Chen, Xin Zhao
Diabetic patients present high co-morbidities of neuropathy and severer consequences of coronary heart disease. But the pathological mechanism is still unclear. Here we investigated a potential association of diabetic impairment of sensory nerves with increase of vulnerability of myocardium in acute myocardial ischemia/reperfusion. A rat model of diabetes mellitus was induced by high fat and sugar diet plus a small dose of streptozotocin. Impairment of sensory nerves was evaluated by measurement of changes in tail flick latency to noxious thermal stimulation and calcitonin gene-related peptide (CGRP) and substance P (SP) in the dorsal root ganglia (DRG) and the myocardium of the heart were examined...
August 26, 2017: Peptides
https://www.readbyqxmd.com/read/28843858/tlr7-deficiency-contributes-to-attenuated-diabetic-retinopathy-via-inhibition-of-inflammatory-response
#12
Yun-Ru Liao, Zi-Jing Li, Peng Zeng, Yu-Qing Lan
Diabetic retinopathy (DR) is a major microvascular complication of diabetes, resulting in neuronal dysfunction, retinal vascular leakage, and apoptosis within the retina. Innate immunity plays an important role in the pathogenesis of type 2 diabetes (T2D) and related complications. The toll-like receptors (TLRs), central to innate immunity, are essential participants in the progression and pathogenesis of the disease and its complications. In the study, streptozotocin (STZ) was combined with whole-body hypoxia for quicker induction of early-stage diabetic retinopathy (DR) in the wild type (WT) and TLR7-knockout (KO) C57BL/6 mice...
August 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28842630/results-from-11-c-metformin-pet-scans-tissue-analysis-and-cellular-drug-sensitivity-assays-questions-the-view-that-biguanides-affects-tumor-respiration-directly
#13
Ane B Iversen, Michael R Horsman, Steen Jakobsen, Jonas B Jensen, Christian Garm, Niels Jessen, Peter Breining, Jørgen Frøkiær, Morten Busk
The anti-diabetic biguanide drugs metformin (METF) and phenformin (PHEN) may have anti-cancer effects. Biguanides suppress plasma growth factors, but nonetheless, the view that these mitochondrial inhibitors accumulate in tumor tissue to an extent that leads to severe energetic stress or alleviation of hypoxia-induced radioresistance is gaining ground. Our cell studies confirm that biguanides inhibits cell proliferation by targeting respiration, but only at highly suprapharmacological concentrations due to low drug retention...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28840975/cardioprotection-mediated-by-exosomes-is-impaired-in-the-setting-of-type-ii-diabetes-but-can-be-rescued-by-the-use-of-non-diabetic-exosomes-in-vitro
#14
Sean M Davidson, Jaime A Riquelme, Kaloyan Takov, Jose M Vicencio, Claire Boi-Doku, Vanessa Khoo, Christian Doreth, Dina Radenkovic, Sergio Lavandero, Derek M Yellon
Many patients with ischaemic heart disease also have diabetes. As myocardial infarction is a major cause of mortality and morbidity in these patients, treatments that increase cell survival in response to ischaemia and reperfusion are needed. Exosomes-nano-sized, lipid vesicles released from cells-can protect the hearts of non-diabetic rats. We previously showed that exosomal HSP70 activates a cardioprotective signalling pathway in cardiomyocytes culminating in ERK1/2 and HSP27 phosphorylation. Here, we investigated whether the exosomal cardioprotective pathway remains intact in the setting of type II diabetes...
August 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28834376/nephropathies
#15
EDITORIAL
Anika Westphal, Stefanie Reuter, Ralf Mrowka
Origins and progresses of nephropathies are manifold and include inflammatory or non-inflammatory causes. The incidence of nephropathies increases all over the world, supported by the growing elderly population. Nowadays there are about two million fatalities per year due to acute kidney injury (AKI) (1) . Clinical outcomes of AKI have not improved over the past 50 years (2) . Renal tissue hypoperfusion and hypoxia are thought to be the main elements causing AKI and the progression to chronic kidney disease (CKD) and end stage renal disease (ESRD) (1) ...
August 18, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28832685/oxygen-environment-and-islet-size-are-the-primary-limiting-factors-of-isolated-pancreatic-islet-survival
#16
Hirotake Komatsu, Colin Cook, Chia-Hao Wang, Leonard Medrano, Henry Lin, Fouad Kandeel, Yu-Chong Tai, Yoko Mullen
BACKGROUND: Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells in the pancreas. Pancreatic islet transplantation could be an effective treatment option for type 1 diabetes once several issues are resolved, including donor shortage, prevention of islet necrosis and loss in pre- and post-transplantation, and optimization of immunosuppression. This study seeks to determine the cause of necrotic loss of isolated islets to improve transplant efficiency. METHODOLOGY: The oxygen tension inside isolated human islets of different sizes was simulated under varying oxygen environments using a computational in silico model...
2017: PloS One
https://www.readbyqxmd.com/read/28832635/expression-of-the-angiogenic-mediator-angiopoietin-like-4-in-the-eyes-of-patients-with-proliferative-sickle-retinopathy
#17
Kathleen Jee, Murilo Rodrigues, Fabiana Kashiwabuchi, Brooks P Applewhite, Ian Han, Gerard Lutty, Morton F Goldberg, Gregg L Semenza, Silvia Montaner, Akrit Sodhi
The recent success of therapies directly targeting the angiogenic mediator, vascular endothelial growth factor (VEGF), for the treatment of proliferative diabetic retinopathy has encouraged clinicians to extend the use of anti-VEGF therapies for the treatment of another ischemic retinal vascular disease, proliferative sickle cell retinopathy (PSR), the most common cause of irreversible blindness in patients with sickle cell disease. However, results from case reports evaluating anti-VEGF therapies for PSR have been mixed...
2017: PloS One
https://www.readbyqxmd.com/read/28832184/type-1-diabetes-at-high-altitude-performance-of-personal-insulin-pumps-and-patient-metabolic-control
#18
Bartłomiej Matejko, Andrzej Gawrecki, Marta Wróbel, Jerzy Hohendorff, Teresa Benbenek-Klupa, Maciej T Malecki, Dorota Zozulińska-Ziółkiewicz, Tomasz Klupa
High-altitude trekking can expose people to extreme environmental conditions, like low temperatures and hypobaric hypoxia. Such extreme conditions make it more difficult for people with type 1 diabetes mellitus (T1DM) to maintain glycemic control. Intensive blood glucose monitoring using either glucose meters or continuous systems is imperative in these cases. In this observational study, we report metabolic control of T1DM patients and the performance of various insulin pumps at high altitude. All 19 patients with T1DM included in this study participated in the final step of the "5000 meters above sugar level" initiative, which involved trekking Damavand Mountain to an altitude of 5670 meters above sea level...
August 23, 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/28826228/carbon-monoxide-inhibits-islet-apoptosis-via-induction-of-autophagy
#19
Do-Sung Kim, Lili Song, Jingjing Wang, Hongju Wu, Wenyu Gou, Wanxing Cui, Jae-Sung Kim, Hongjun Wang
AIM: Carbon monoxide (CO) functions as a therapeutic molecule in various disease models because of its anti-inflammatory and anti-apoptotic properties. We investigated the capacity of CO to reduce hypoxia-induced islet cell death and dysfunction in human and mouse models. RESULTS: Culturing islets in CO-saturated medium protected them from hypoxia-induced apoptosis, and preserved β cell function by suppressing expression of pro-apoptotic (Bim, PARP, Cas-3), pro-inflammatory (TNF-α), and ER stress (glucose-regulated protein 94, grp94, CHOP) proteins...
August 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28821742/rock-1-mediates-diabetes-induced-retinal-pigment-epithelial-and-endothelial-cell-blebbing-contribution-to-diabetic-retinopathy
#20
Pierre-Raphaël Rothschild, Sawsen Salah, Marianne Berdugo, Emmanuelle Gélizé, Kimberley Delaunay, Marie-Christine Naud, Christophe Klein, Alexandre Moulin, Michèle Savoldelli, Ciara Bergin, Jean-Claude Jeanny, Laurent Jonet, Yvan Arsenijevic, Francine Behar-Cohen, Patricia Crisanti
In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers...
August 18, 2017: Scientific Reports
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