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Akita mice

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https://www.readbyqxmd.com/read/29061652/progressive-renal-disease-established-by-renin-coding-adeno-associated-virus-driven-hypertension-in-diverse-diabetic-models
#1
Shannon M Harlan, Kathleen M Heinz-Taheny, John M Sullivan, Tao Wei, Hana E Baker, Dianna L Jaqua, Zhonghua Qi, Martin S Cramer, Tatiyana L Shiyanova, Matthew D Breyer, Josef G Heuer
Progress in research and developing therapeutics to prevent diabetic kidney disease (DKD) is limited by a lack of animal models exhibiting progressive kidney disease. Chronic hypertension, a driving factor of disease progression in human patients, is lacking in most available models of diabetes. We hypothesized that superimposition of hypertension on diabetic mouse models would accelerate DKD. To test this possibility, we induced persistent hypertension in three mouse models of type 1 diabetes and two models of type 2 diabetes by adeno-associated virus delivery of renin (ReninAAV)...
October 23, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29043461/effect-of-anti-angiogenesis-induced-by-chemotherapeutic-monotherapy-chemotherapeutic-bisphosphonate-combination-therapy-and-anti-vegfa-mab-therapy-on-tooth-extraction-socket-healing-in-mice
#2
Yuri Akita, Shinichiro Kuroshima, Kazunori Nakajima, Hiroki Hayano, Riho Kanai, Muneteru Sasaki, Takashi Sawase
Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of this study was to determine the precise etiology of ONJ induced by chemotherapy and bisphosphonate combination therapy. Mice received zoledronate (ZA) monotherapy, cyclophosphamide (CY) monotherapy or CY/ZA combination therapy...
October 17, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28883608/gyy4137-a-hydrogen-sulfide-donor-modulates-mir194-dependent-collagen-realignment-in-diabetic-kidney
#3
A M Sashi Papu John, Sourav Kundu, Sathnur Pushpakumar, Maura Fordham, Gregory Weber, Manas Mukhopadhyay, Utpal Sen
The relationship between hydrogen sulfide (H2S), microRNAs (miRs), matrix metalloproteinases (MMPs) and poly-ADP-ribose-polymerase-1 (PARP-1) in diabetic kidney remodeling remains mostly obscured. We aimed at investigating whether alteration of miR-194-dependent MMPs and PARP-1 causes renal fibrosis in diabetes kidney, and whether H2S ameliorates fibrosis. Wild type, diabetic Akita mice as well as mouse glomerular endothelial cells (MGECs) were used as experimental models, and GYY4137 as H2S donor. In diabetic mice, plasma H2S levels were decreased while ROS and expression of its modulator (ROMO1) were increased...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837672/cardiac-transcriptome-profiling-of-diabetic-akita-mice-using-microarray-and-next-generation-sequencing
#4
Varun Kesherwani, Hamid R Shahshahan, Paras K Mishra
Although diabetes mellitus (DM) causes cardiomyopathy and exacerbates heart failure, the underlying molecular mechanisms for diabetic cardiomyopathy/heart failure are poorly understood. Insulin2 mutant (Ins2+/-) Akita is a mouse model of T1DM, which manifests cardiac dysfunction. However, molecular changes at cardiac transcriptome level that lead to cardiomyopathy remain unclear. To understand the molecular changes in the heart of diabetic Akita mice, we profiled cardiac transcriptome of Ins2+/- Akita and Ins2+/+ control mice using next generation sequencing (NGS) and microarray, and determined the implications of differentially expressed genes on various heart failure signaling pathways using Ingenuity pathway (IPA) analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28686632/autophagy-dependent-regulation-of-tumor-metastasis-by-myeloid-cells
#5
Masahisa Jinushi, Tomoko Morita, Zhihang Xu, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Hideo Yagita, Yutaka Kawakami
Autophagy is a vital process controlling the lysosomal degradation of cellular organelles and thereby regulating tissue homeostasis in an environment-dependent fashion. Recent studies have unveiled the critical role of tumor cell-derived autophagy in regulating pro-tumor and anti-tumor processes depending on different stages and tumor microenvironments. However, the precise mechanism whereby autophagy regulates tumor progression remains largely unclear. Since myeloid cells contribute to tumor progression and metastasis, we evaluated the role of myeloid cell-specific autophagy in the regulation of tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28598529/association-of-a-reactive-intermediate-derived-from-1-6-dihydroxy-metabolite-with-benzbromarone-induced-hepatotoxicity
#6
Mina Yoshida, Naoki Cho, Hidetaka Akita, Kaoru Kobayashi
Treatment with benzbromarone can be associated with liver injury, but the detailed mechanism remains unknown. Our recent studies demonstrated that benzbromarone was metabolized to 1',6-dihydroxybenzbromarone and followed by formation of reactive intermediates that were trapped by glutathione, suggesting that the reactive intermediates may be responsible for the liver injury. The aim of this study was to clarify whether the reactive intermediates derived from 1',6-dihydroxybenzbromarone is a risk factor of liver injury in mice...
June 9, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28535269/increased-retinal-oxygen-metabolism-precedes-microvascular-alterations-in-type-1-diabetic-mice
#7
Wenzhong Liu, Shoujian Wang, Brian Soetikno, Ji Yi, Kevin Zhang, Siyu Chen, Robert A Linsenmeier, Christine M Sorenson, Nader Sheibani, Hao F Zhang
Purpose: To investigate inner retinal oxygen metabolic rate (IRMRO2) during early stages of type 1 diabetes in a transgenic mouse model. Methods: In current study, we involved seven diabetic mice (Akita/+, TSP1-/-) and seven control mice (TSP1-/-), and applied visible-light optical coherence tomography (vis-OCT) to image functional parameters including retinal blood flow rate, oxygen saturation (sO2) and the IRMRO2 value longitudinally from 5 weeks of age to 13 weeks of age...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28522367/qrs-t-wave-and-calcium-alternans-in-a-type-i-diabetic-mouse-model-for-spontaneous-postmyocardial-infarction-ventricular-tachycardia-a-mechanism-for-the-antiarrhythmic-effect-of-statins
#8
Hongwei Jin, Charles M Welzig, Mark Aronovitz, Farzad Noubary, Robert Blanton, Bo Wang, Mohammad Rajab, Alfred Albano, Mark S Link, Sami F Noujaim, Ho-Jin Park, Jonas B Galper
BACKGROUND: The incidence of sudden arrhythmic death is markedly increased in diabetics. OBJECTIVE: The purpose of this study was to develop a mouse model for postmyocardial infarction (post-MI) ventricular tachycardia (VT) in the diabetic heart and determine the mechanism of an antiarrhythmic effect of statins. METHODS: ECG transmitters were implanted in wild-type (WT), placebo, and pravastatin-treated type I diabetic Akita mice. MIs were induced by coronary ligation, and Ca(2+) transients were studied by optical mapping, and Ca(2+) transients and sparks in left ventricular myocytes (VM) by the Ionoptix system and confocal microscopy...
September 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28508291/lobular-homology-in-cerebellar-hemispheres-of-humans-non-human-primates-and-rodents-a-structural-axonal-tracing-and-molecular-expression-analysis
#9
REVIEW
Yuanjun Luo, Hirofumi Fujita, Hermina Nedelescu, Mohammad Shahangir Biswas, Chika Sato, Sarah Ying, Mayu Takahashi, Keiichi Akita, Tatsuya Higashi, Ichio Aoki, Izumi Sugihara
Comparative neuroanatomy provides insights into the evolutionary functional adaptation of specific mammalian cerebellar lobules, in which the lobulation pattern and functional localization are conserved. However, accurate identification of homologous lobules among mammalian species is challenging. In this review, we discuss the inter-species homology of crus I and II lobules which occupy a large volume in the posterior cerebellar hemisphere, particularly in humans. Both crus I/II in humans are homologous to crus I/II in non-human primates, according to Paxinos and colleagues; however, this area has been defined as crus I alone in non-human primates, according to Larsell and Brodal...
May 15, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28493939/inhibition-of-nitric-oxide-production-reverses-diabetes-induced-kupffer-cell-activation-and-klebsiella-pneumonia-liver-translocation
#10
Shu-Han Lin, Pei-Hsuan Chung, Ying-Ying Wu, Chang-Phone Fung, Ching-Mei Hsu, Lee-Wei Chen
Klebsiella pneumoniae (KP) is the most common pathogen of pyogenic liver abscess in East and Southeast Asia and diabetes mellitus (DM) is a major risk factor. The effect and mechanism of diabetes on KP liver abscess was examined in streptozotocin-induced diabetic mice and Akita mice (C57BL/6J-Ins2Akita). KP translocation to liver and plasma alaine transaminase levels were increased and liver clearance of KP was decreased in DM mice. Diabetic mice exhibited overgrowth of Enterococcus as well as E.coli and decreased lactobacilli/bifidas growth in intestine, increased intestinal iNOS protein and nitrite levels in portal vein, and increased IL-1β and TNF-α expression of Kupffer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28490532/podocyte-specific-knockout-of-cyclooxygenase-2-exacerbates-diabetic-kidney-disease
#11
Liming Wang, Yonggang Sha, Jingyi Bai, William Eisner, Matthew A Sparks, Anne F Buckley, Robert F Spurney
Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to glomerular injury in diabetic kidney disease, but some basal level of podocyte COX2 expression might be required to promote podocyte attachment and/or survival. To investigate the role of podocyte COX2 expression in diabetic kidney disease, we deleted COX2 specifically in podocytes in a mouse model of Type 1 diabetes mellitus (Akita mice). Podocyte-specific knockout (KO) of COX2 did not affect renal morphology or albuminuria in nondiabetic mice...
August 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28432078/effect-of-4-5-6-7-8-tetrahydro-5-5-8-8-tetramethyl-2-naphthalenyl-carbamoyl-benzoic-acid-am80-on-alveolar-regeneration-in-adiponectin-deficient-mice-showing-a-chronic-obstructive-pulmonary-disease-like-pathophysiology
#12
Hitomi Sakai, Michiko Horiguchi, Tomomi Akita, Chihiro Ozawa, Mai Hirokawa, Yuki Oiso, Harumi Kumagai, Yoshito Takeda, Isao Tachibana, Norikazu Maeda, Chikamasa Yamashita
Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease that causes widespread and irreversible alveolar collapse. Although COPD occurs worldwide, only symptomatic therapy is currently available. Our objective is the development of therapeutic agents to eradicate COPD. Therefore, we focused on 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid (Am80), which is a derivative of all-trans retinoic acid. We evaluated the effects of Am80 on alveolar repair in a novel COPD model of adiponectin-deficient mice...
June 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28353063/the-microrna-7-mediated-reduction-in-epac-1-contributes-to-vascular-endothelial-permeability-and-enos-uncoupling-in-murine-experimental-retinopathy
#13
Veronica Garcia-Morales, Julian Friedrich, Lysanne M Jorna, Manuel Campos-Toimil, Hans-Peter Hammes, Martina Schmidt, Guido Krenning
AIMS: To investigate the consequences of oxidative stress and hypoxia on EPAC-1 expression during retinopathy. METHODS: Oxygen-induced retinopathy was induced in mice and EPAC-1 expression investigated by immunofluorescence. In silico analyses were used to identify a link between EPAC-1 expression and microRNA-7-5p in endothelial cells and confirmed by western blot analyses on cells expressing microRNA-7-5p. In vitro, endothelial cells were either incubated at 2% oxygen or transfected with microRNA-7-5p, and the effects of these treatments on EPAC-1 expression, endothelial hyperpermeability and NO production were assessed...
June 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28324005/insulin-inhibits-nrf2-gene-expression-via-heterogeneous-nuclear-ribonucleoprotein-f-k-in-diabetic-mice
#14
Anindya Ghosh, Shaaban Abdo, Shuiling Zhao, Chin-Han Wu, Yixuan Shi, Chao-Sheng Lo, Isabelle Chenier, Thierry Alquier, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
Oxidative stress induces endogenous antioxidants via nuclear factor erythroid 2-related factor 2 (Nrf2), potentially preventing tissue injury. We investigated whether insulin affects renal Nrf2 expression in type 1 diabetes (T1D) and studied its underlying mechanism. Insulin normalized hyperglycemia, hypertension, oxidative stress, and renal injury; inhibited renal Nrf2 and angiotensinogen (Agt) gene expression; and upregulated heterogeneous nuclear ribonucleoprotein F and K (hnRNP F and hnRNP K) expression in Akita mice with T1D...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28259677/soluble-epoxide-hydrolase-inhibition-alleviates-neuropathy-in-akita-ins2-akita-mice
#15
Karen Wagner, Jennifer Gilda, Jun Yang, Debin Wan, Christophe Morisseau, Aldrin V Gomes, Bruce D Hammock
The soluble epoxide hydrolase (sEH) is a regulatory enzyme responsible for the metabolism of bioactive lipid epoxides of both omega-6 and omega-3 long chain polyunsaturated fatty acids. These natural epoxides mediate cell signaling in several physiological functions including blocking inflammation, high blood pressure and both inflammatory and neuropathic pain. Inhibition of the sEH maintains the level of endogenous bioactive epoxy-fatty acids (EpFA) and allows them to exert their generally beneficial effects...
May 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28253885/the-nuclear-factor-erythroid-derived-2-like-2-nrf2-activator-dh404-protects-against-diabetes-induced-endothelial-dysfunction
#16
Arpeeta Sharma, Luddwi Rizky, Nada Stefanovic, Mitchel Tate, Rebecca H Ritchie, Keith W Ward, Judy B de Haan
BACKGROUND: Vascular dysfunction is a pivotal event in the development of diabetes-associated vascular disease. Increased inflammation and oxidative stress are major contributors to vascular dysfunction. Nrf2, a master regulator of several anti-oxidant genes and a suppressor of inflammatory NF-κB, has potential as a target to combat oxidative stress and inflammation. The aim of this study was to investigate the effects of a novel Nrf2 activator, the bardoxolone methyl derivative dh404, on endothelial function in vitro and in vivo...
March 3, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28214591/hyperglycemia-is-associated-with-reduced-testicular-function-and-activin-dysregulation-in-the-ins2-akita-mouse-model-of-type-1-diabetes
#17
Constanze C Maresch, Dina C Stute, Helen Ludlow, Hans-Peter Hammes, David M de Kretser, Mark P Hedger, Thomas Linn
Type 1 diabetes (T1D) is associated with subfertility in men. We hypothesised that this results from inhibitory effects of chronic hyperglycemia on testicular function and used the Ins2(Akita+/-) mouse model to investigate this. Diabetic mice exhibited progressive testicular dysfunction, with a 30% reduction in testis weight at 24 weeks of age. Diabetic mice showed significantly reduced seminiferous tubule diameters and increased spermatogenic disruption, although testes morphology appeared grossly normal. Unexpectedly, serum LH and intra-testicular testosterone were similar in all groups...
May 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28210739/retinal-oxidative-stress-at-the-onset-of-diabetes-determined-by-synchrotron-ftir-widefield-imaging-towards-diabetes-pathogenesis
#18
Ebrahim Aboualizadeh, Mahsa Ranji, Christine M Sorenson, Reyhaneh Sepehr, Nader Sheibani, Carol J Hirschmugl
Diabetic retinopathy is a microvascular complication of diabetes that can lead to blindness. In the present study, we aimed to determine the nature of diabetes-induced, highly localized biochemical changes in the neuroretina at the onset of diabetes. High-resolution synchrotron Fourier transform infrared (s-FTIR) wide field microscopy coupled with multivariate analysis (PCA-LDA) was employed to identify biomarkers of diabetic retinopathy with spatial resolution at the cellular level. We compared the retinal tissue prepared from 6-week-old Ins2(Akita/+) heterozygous (Akita/+, N = 6; a model of diabetes) male mice with the wild-type (control, N = 6) mice...
March 27, 2017: Analyst
https://www.readbyqxmd.com/read/28154187/decreased-mitochondrial-pyruvate-transport-activity-in-the-diabetic-heart-role-of-mitochondrial-pyruvate-carrier-2-mpc2-acetylation
#19
Shraddha S Vadvalkar, Satoshi Matsuzaki, Craig A Eyster, Jennifer R Giorgione, Lee B Bockus, Caroline S Kinter, Michael Kinter, Kenneth M Humphries
Alterations in mitochondrial function contribute to diabetic cardiomyopathy. We have previously shown that heart mitochondrial proteins are hyperacetylated in OVE26 mice, a transgenic model of type 1 diabetes. However, the universality of this modification and its functional consequences are not well established. In this study, we demonstrate that Akita type 1 diabetic mice exhibit hyperacetylation. Functionally, isolated Akita heart mitochondria have significantly impaired maximal (state 3) respiration with physiological pyruvate (0...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28116093/inhibition-of-sglt2-alleviates-diabetic-nephropathy-by-suppressing-high-glucose-induced-oxidative-stress-in-type-1-diabetic-mice
#20
Takashi Hatanaka, Daisuke Ogawa, Hiromi Tachibana, Jun Eguchi, Tatsuyuki Inoue, Hiroshi Yamada, Kohji Takei, Hirofumi Makino, Jun Wada
It is unclear whether the improvement in diabetic nephropathy by sodium glucose cotransporter 2 (SGLT2) inhibitors is caused by a direct effect on SGLT2 or by the improvement in hyperglycemia. Here, we investigated the effect of dapagliflozin on early-stage diabetic nephropathy using a mouse model of type 1 diabetes and murine proximal tubular epithelial cells. Eight-week-old Akita mice were treated with dapagliflozin or insulin for 12 weeks. Body weight, urinary albumin excretion, blood pressure, as well as levels of blood glucose and hemoglobin A1c were measured...
August 2016: Pharmacology Research & Perspectives
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