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Hypoxia Insulin

Ingrid K Hals, Rinku Singh, Zuheng Ma, Hanne Scholz, Anneli Björklund, Valdemar Grill
We tested whether exposure of beta cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike...
October 20, 2016: Islets
Jeffrey I Mechanick, Shan Zhao, W Timothy Garvey
Adipokines are peptides, secreted by adipocytes and other cell types with targets in other tissues, participating in a complex network of humoral factors involved in obesity, insulin resistance, and cardiovascular (CV) disease. This review describes recent information about adipokine effects on the CV system. Rather than simply providing a listing of adipokines and their respective effects, network analysis is used to enhance understanding. Various relationships and emergent processes in the adipokine-CV system network are discussed, with the most significant interactors being responses to hypoxia, regulation of cell migration, effects on blood coagulation, and platelet activation...
October 18, 2016: Journal of the American College of Cardiology
Changhwan Ahn, Dongoh Lee, Jae-Hwan Lee, Hyun Yang, Beum-Soo An, Eui-Bae Jeung
It has been proposed that cellular Ca2+ signals activate hormone secretion. In pancreatic β cells, which produce insulin, Ca2+ signals have been known to contribute to insulin secretion. Prior to this study, we confirmed that insulin-secreting β cells express CaBP-9k, and assumed that CaBP-9k play a role in β cell insulin synthesis or secretion. Using CaBP-9k knock out (KO) mice, we demonstrated that ablation of CaBP-9k causes reducing insulin secretion and increasing serum glucose. To compare the role of CaBP-9k with pathophysiological conditions, we exposed wild-type and CaBP-9k KO mice to hypoxic conditions for 10 days...
2016: PloS One
Patience Meo Burt, Liping Xiao, Caroline Dealy, Melanie C Fisher, Marja M Hurley
Humans with X-linked hypophosphatemia (XLH) and Hyp mice, the murine homologue of the disease, develop severe osteoarthropathy and the precise factors that contribute to this joint degeneration remain largely unknown. Fibroblast growth factor 2 (FGF2) is a key regulatory growth factor in osteoarthritis. Although there are multiple FGF2 isoforms the potential involvement of specific FGF2 isoforms in joint degradation has not been investigated. Mice that overexpress the high molecular weight FGF2 isoforms in bone (HMWTg mice) phenocopy Hyp mice and XLH subjects and Hyp mice overexpress the HMWFGF2 isoforms in osteoblasts and osteocytes...
October 12, 2016: Endocrinology
Keri S Taylor, Hisayoshi Murai, Philip J Millar, Nobuhiko Haruki, Derek S Kimmerly, Beverley L Morris, George Tomlinson, T Douglas Bradley, John S Floras
Obstructive apnea during sleep elevates the set point for efferent sympathetic outflow during wakefulness. Such resetting is attributed to hypoxia-induced upregulation of peripheral chemoreceptor and brain stem sympathetic function. Whether recurrent arousal from sleep also influences daytime muscle sympathetic nerve activity is unknown. We therefore tested, in a cohort of 48 primarily nonsleepy, middle-aged, male (30) and female (18) volunteers (age: 59±1 years, mean±SE), the hypothesis that the frequency of arousals from sleep (arousal index) would relate to daytime muscle sympathetic burst incidence, independently of the frequency of apnea or its severity...
October 3, 2016: Hypertension
Liza Margareth Sousa, Renata Silva, Vanessa Fonseca, Rafael Leandro, Thiago Di Vincenzo, Ana Bárbara Alves-Wagner, Ubiratan Fabres Machado, Paula Papa
This study aimed to determine in the canine corpus luteum throughout the diestrus: 1) the influence of insulin on glucose utilization; 2) the regulation of genes potentially involved; and 3) the influence of hypoxia on glucose transporter expression and steroidogenesis, after treatment with cobalt chloride (CoCl2). Glucose uptake by luteal cells increased 2.7 folds (P<0.05) in response to insulin; a phenomenon related to increased expression of glucose transporter (GLUT) 4 and phosphorylation of protein kinase B (AKT)...
September 27, 2016: Journal of Endocrinology
Alaa Shafie, Mingzhan Xue, Guy Barker, Daniel Zehnder, Paul J Thornalley, Naila Rabbani
Glyoxalase 1 (Glo1) is a cytoplasmic enzyme with a cytoprotective function linked to metabolism of the cytotoxic side-product of glycolysis, methylglyoxal. It prevents dicarbonyl stress - the abnormal accumulation of reactive dicarbonyl metabolites increasing protein and DNA damage. Increased Glo1 expression delays ageing and suppresses carcinogenesis, insulin resistance, cardiovascular disease and vascular complications of diabetes and renal failure. Surprisingly gene trapping by the International Mouse Knockout Consortium (IMKC) to generate putative Glo1 knockout mice produced a mouse line with phenotype characterised as normal and healthy...
September 26, 2016: Biochemical Journal
Ashley L Gehrand, Brian Hoeynck, Mack Jablonski, Cole Leonovicz, Risheng Ye, Philipp E Scherer, Hershel Raff
Acute neonatal hypoxia, a common stressor, causes a spontaneous decrease in body temperature which may be protective. There is consensus that hypothermia should be prevented during acute hypoxia in the human neonate; however, this may be an additional stress with negative consequences. We hypothesize that maintaining body temperature during hypoxia in the first week of postnatal life alters the subsequent insulin, glucose, and glucagon secretion in adult rats. Rat pups were separated from their dam daily from postnatal days (PD) 2-6 for the following 90 min experimental treatments: (1) normoxic separation (control), (2) hypoxia (8% O2) allowing spontaneous hypothermia, (3) normoxic hypothermia with external cold, and (4) exposure to 8% O2 while maintaining body temperature using external heat...
September 2016: Physiological Reports
Liske M Kotzé-Hörstmann, Dheshnie Keswell, Kevin Adams, Thandiwe Dlamini, Julia H Goedecke
Black South African women are more insulin resistant and have increased gluteal subcutaneous adipose tissue hypertrophy than white South African women. We tested the hypothesis that adipose tissue hypoxia and extracellular matrix gene expression in gluteal and abdominal subcutaneous adipose tissue is higher in black than white women, and associates with reduced insulin sensitivity in black women. Insulin sensitivity (frequently sampled intravenous glucose tolerance test), gluteal and abdominal subcutaneous adipose tissue mRNA levels of hypoxia- and extracellular matrix-related genes were measured in normal-weight and obese premenopausal black (n = 30) and white (n = 26) South African women at baseline, and in black women, at 5-year follow-up (n = 10)...
September 14, 2016: Endocrine
Akiko Takikawa, Arshad Mahmood, Allah Nawaz, Tomonobu Kado, Keisuke Okabe, Seiji Yamamoto, Aminuddin Arif, Satoko Senda, Koichi Tsuneyama, Masashi Ikutani, Yasuharu Watanabe, Yoshiko Igarashi, Yoshinori Nagai, Kiyoshi Takatsu, Keiichi Koizumi, Johji Imura, Nobuhito Goda, Masakiyo Sasahara, Michihiro Matsumoto, Kumiko Saeki, Takashi Nakagawa, Shiho Fujisaka, Isao Usui, Kazuyuki Tobe
Adipose tissue hypoxia is an important feature of pathological adipose tissue expansion. Hypoxia-inducible factor-1α (HIF-1α) in adipocytes reportedly induces oxidative stress and fibrosis, rather than neoangiogenesis via VEGF-A. We previously reported that macrophages in crown-like structures (CLSs) are both hypoxic and inflammatory. In the present study, we examined how macrophage HIF-1α is involved in high-fat diet (HFD)-induced inflammation, neovascularization, hypoxia, and insulin resistance using mice with myeloid cell-specific HIF-1α deletion fed an HFD...
September 13, 2016: Diabetes
Anne Briançon-Marjollet, Denis Monneret, Marion Henri, Marie Joyeux-Faure, Perle Totoson, Sandrine Cachot, Patrice Faure, Diane Godin-Ribuot
What is the central question of this study? This study addresses the relative impact of obesity and intermittent hypoxia in the pathophysiological process of obstructive sleep apnoea by investigating the metabolic, inflammatory and cardiovascular consequences of intermittent hypoxia in lean and obese Zucker rats. What is the main finding and its importance? We found that obesity and intermittent hypoxia have mainly distinct consequences on the investigated inflammatory and cardiometabolic parameters in Zucker rats...
October 5, 2016: Experimental Physiology
Bhawna Chandravanshi, Ramesh Bhonde
Transplantation of pancreatic islets is the most reliable treatment for Type 1 diabetes. However cell death mediated by hypoxia is considered as one of the main difficulties hindering success in islet transplantation. The aim of our experiment was to investigate the role of small molecules in survival of Islet like cell aggregates (ICAs) engineered from umbilical cord matrix under oxygen deprived condition (<5% O2). ICAs were analyzed for cell death via fluoroscein diacetate/propidium iodide (FDA/PI) staining, estimation of Caspase 3 and free radical release in presence and absence of small molecules...
September 8, 2016: European Journal of Pharmacology
Ailsa Maria Main, Linn Gillberg, Anna Louisa Jacobsen, Emma Nilsson, Anette Prior Gjesing, Torben Hansen, Oluf Pedersen, Rasmus Ribel-Madsen, Allan Vaag
BACKGROUND: Associations between BMI and DNA methylation of hypoxia-inducible factor 3-alpha (HIF3A) in both blood cells and subcutaneous adipose tissue (SAT) have been reported. In this study, we investigated associations between BMI and HIF3A DNA methylation in the blood and SAT from the same individuals, and whether HIF3A gene expression in SAT and skeletal muscle biopsies showed associations with BMI and insulin resistance. Furthermore, we aimed to investigate gender specificity and heritability of these traits...
2016: Clinical Epigenetics
Shogo Kuwagata, Shinji Kume, Masami Chin-Kanasaki, Hisazumi Araki, Shinichi Araki, Jun Nakazawa, Takeshi Sugaya, Daisuke Koya, Masakazu Haneda, Hiroshi Maegawa, Takashi Uzu
Hypoxia causes proximal tubular cell damage in diabetes, even though proximal tubular cells have an adaptive system to combat hypoxia involving induction of hypoxia factor-1 (HIF-1) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). Here, we examined the interference effect of altered glucose and lipid metabolism on the hypoxia responses in proximal tubular cells. In culture, hypoxia alone induced HIF-1 and inhibited mTORC1, preventing death in proximal tubular cells. However, hypoxia with high glucose and palmitate increased mTORC1 activity and promoted apoptosis in proximal tubular cells, which was inhibited by pharmacological and genetic inactivation of mTORC1...
August 30, 2016: Kidney International
E L Peters, C Offringa, D Kos, W J Van der Laarse, R T Jaspers
A major problem in chronic heart failure is the inability of hypertrophied cardiomyocytes to maintain the required power output. A Hill-type oxygen diffusion model predicts that oxygen supply is limiting in hypertrophied cardiomyocytes at maximal rates of oxygen consumption and that this limitation can be reduced by increasing the myoglobin (Mb) concentration. We explored how cardiac hypertrophy, oxidative capacity, and Mb expression in right ventricular cardiomyocytes are regulated at the transcriptional and translational levels in an early stage of experimental pulmonary hypertension, in order to identify targets to improve the oxygen supply/demand ratio...
October 2016: Pflügers Archiv: European Journal of Physiology
Ji Hye Kim, Sei Mee Yoon, Sun U Song, Sang Gyu Park, Won-Serk Kim, In Guk Park, Jinu Lee, Jong-Hyuk Sung
Hypoxia has diverse stimulatory effects on human adipose-derived stem cells (ASCs). In the present study, we investigated whether hypoxic culture conditions (2% O₂) suppress spontaneous mineralization and osteogenic differentiation of ASCs. We also investigated signaling pathways and molecular mechanisms involved in this process. We found that hypoxia suppressed spontaneous mineralization and osteogenic differentiation of ASCs, and up-regulated mRNA and protein expression of Insulin-like growth factor binding proteins (IGFBPs) in ASCs...
2016: International Journal of Molecular Sciences
Marcel Boß, Yvette Newbatt, Sahil Gupta, Ian Collins, Bernhard Brüne, Dmitry Namgaladze
Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty acids (SFA), and endoplasmic reticulum (ER) stress responses essentially contribute to pro-inflammatory signalling. AMP-activated protein kinase (AMPK) is a central metabolic regulator with established anti-inflammatory actions. Whether pharmacological AMPK activation suppresses SFA-induced inflammation in a human system is unclear...
2016: Scientific Reports
Xuanchun Wang, Samuel M Lockhart, Thomas Rathjen, Hassan Albadawi, Ditte Sørensen, Brian T O'Neill, Nishant Dwivedi, Simone R Preil, Hans Christian Beck, Sally L Dunwoodie, Michael T Watkins, Lars Melholt Rasmussen, Christian Rask-Madsen
In patients with atherosclerotic complications of diabetes, impaired neovascularization of ischemic tissue in the myocardium and lower limb limits the ability of these tissues to compensate for poor perfusion. We identified 10 novel insulin-regulated genes, among them Adm, Cited2 and Ctgf, which were downregulated in endothelial cells by insulin through FoxO1. CITED2, which was downregulated by insulin by up to 54%, is an important negative regulator of hypoxia-inducible factor (HIF) and impaired HIF signaling is a key mechanism underlying the impairment of angiogenesis in diabetes...
August 25, 2016: Diabetes
Dmytro O Minchenko, A P Kharkova, O V Halkin, L L Karbovskyi, O H Minchenko
OBJECTIVE: The aim of the present study was to investigate the effect of hypoxia on the expression of genes encoding insulin-like growth factors (IGF1 and IGF2), their receptor (IGF1R), binding protein-4 (IGFBP4), and stanniocalcin 2 (STC2) in U87 glioma cells in relation to inhibition of endoplasmic reticulum stress signaling mediated by IRE1 (inositol requiring enzyme 1) for evaluation of their possible significance in the control of tumor growth. METHODS: The expression of IGF1, IGF2, IGF1R, IGFBP4, and STC2 genes in U87 glioma cells transfected by empty vector pcDNA3...
April 2016: Endocrine Regulations
Nicola Jeffery, Lorna W Harries
Type 2 diabetes (T2D) affects 415 million people worldwide and is characterized by chronic hyperglycaemia and insulin resistance, progressing to insufficient insulin production, as a result of β-cell failure. Over time, chronic hyperglycaemia can ultimately lead to loss of β-cell function, leaving patients insulin-dependent. Until recently the loss of β-cell mass seen in T2D was considered to be the result of increased rates of apoptosis; however, it has been proposed that apoptosis alone cannot account for the extent of β-cell mass loss seen in the disease, and that a loss of function may also occur as a result of changes in β-cell differentiation status...
August 23, 2016: Diabetes, Obesity & Metabolism
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