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https://www.readbyqxmd.com/read/28210739/retinal-oxidative-stress-at-the-onset-of-diabetes-determined-by-synchrotron-ftir-widefield-imaging-towards-diabetes-pathogenesis
#1
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...
February 17, 2017: Analyst
https://www.readbyqxmd.com/read/28154187/decreased-mitochondrial-pyruvate-transport-activity-in-the-diabetic-heart-role-of-mpc2-acetylation
#2
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 hyper-acetylated 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 hyper-acetylation. Functionally, isolated Akita heart mitochondria have significantly impaired maximal (state 3) respiration with physiological pyruvate (0...
February 1, 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
#3
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
https://www.readbyqxmd.com/read/28102311/plin2-is-a-key-regulator-of-the-unfolded-protein-response-and-endoplasmic-reticulum-stress-resolution-in-pancreatic-%C3%AE-cells
#4
Elaine Chen, Tsung Huang Tsai, Lan Li, Pradip Saha, Lawrence Chan, Benny Hung-Junn Chang
Progressive pancreatic β cell failure underlies the transition of impaired glucose tolerance to overt diabetes; endoplasmic reticulum (ER) stress expedites β cell failure in this situation. ER stress can be elicited by lipotoxicity and an increased demand for insulin in diabetes. We previously reported that the lipid droplet protein perilipin 2 (PLIN2) modulates lipid homeostasis in the liver. Here, we show that PLIN2 modulates the unfolded protein response (UPR) and ER stress in pancreatic β cells. PLIN2 expression goes up when β cells are exposed to a lipid load or to chemical ER stress inducers...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069641/differential-impact-of-chronic-hyperglycemia-on-humoral-versus-cellular-primary-alloimmunity
#5
Nicholas H Bishop, Michelle K Nelsen, K Scott Beard, Ronald G Gill
Diabetes is prevalent among solid organ transplant recipients and is universal among islet transplant recipients. While diabetes is often considered to result in an immune compromised state, the impact of chronic hyperglycemia on host alloimmunity is not clear. Potential immune modifying effects of obesity, autoimmunity, or diabetogenic agents like streptozotocin may confound understanding alloimmunity in experimental models of diabetes. Therefore, we sought to determine the role of chronic hyperglycemia due to insulinopenia on alloimmunity using the non-autoimmune, spontaneously diabetic H-2(b)-expressing C57BL/6 Ins2(Akita) mice (Akita)...
January 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28017717/preserving-expression-of-pdx1-improves-%C3%AE-cell-failure-in-diabetic-mice
#6
Yuichi Yamamoto, Takeshi Miyatsuka, Shugo Sasaki, Kazuyuki Miyashita, Fumiyo Kubo, Naoki Shimo, Satomi Takebe, Hirotaka Watada, Hideaki Kaneto, Taka-Aki Matsuoka, Iichiro Shimomura
Pdx1, a β-cell-specific transcription factor, has been shown to play a crucial role in maintaining β-cell function through transactivation of β-cell-related genes. In addition, it has been reported that the expression levels of Pdx1 are compromised under diabetic conditions in human and rodent models. We therefore aimed to clarify the possible beneficial role of Pdx1 against β-cell failure and generated the transgenic mouse that expressed Pdx1 conditionally and specifically in β cells (βPdx1) and crossed these mice with Ins2(Akita) diabetic mice...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27980343/il-17a-exacerbates-diabetic-retinopathy-by-impairing-m%C3%A3-ller-cell-function-via-act1-signaling
#7
Ao-Wang Qiu, Zheng Bian, Ping-An Mao, Qing-Huai Liu
Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2(Akita) (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells...
December 16, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27914705/pigment-epithelium-derived-factor-a-noninhibitory-serine-protease-inhibitor-is-renoprotective-by-inhibiting-the-wnt-pathway
#8
Xuemin He, Rui Cheng, Kyoungmin Park, Siribhinya Benyajati, Gennadiy Moiseyev, Chengyi Sun, Lorin E Olson, Yanhui Yang, Bonnie K Eby, Kai Lau, Jian-Xing Ma
Pigment epithelium-derived factor (PEDF) expression is downregulated in the kidneys of diabetic rats, and delivery of PEDF suppressed renal fibrotic factors in these animals. PEDF has multiple functions including anti-angiogenic, anti-inflammatory and antifibrotic activities. Since the mechanism underlying its antifibrotic effect remains unclear, we studied this in several murine models of renal disease. Renal PEDF levels were significantly reduced in genetic models of type 1 and type 2 diabetes (Akita and db/db, respectively), negatively correlating with Wnt signaling activity in the kidneys...
March 2017: Kidney International
https://www.readbyqxmd.com/read/27909574/characterization-of-5-2-18-f-fluoroethoxy-l-tryptophan-for-pet-imaging-of-the-pancreas
#9
Ahmed Abbas, Christine Beamish, Rebecca McGirr, John Demarco, Neil Cockburn, Dawid Krokowski, Ting-Yim Lee, Michael Kovacs, Maria Hatzoglou, Savita Dhanvantari
Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2- (18)F-fluoroethoxy)-L-tryptophan ( (18)F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of (18)F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution...
2016: F1000Research
https://www.readbyqxmd.com/read/27881924/rodent-models-of-diabetic-nephropathy-their-utility-and-limitations
#10
REVIEW
Munehiro Kitada, Yoshio Ogura, Daisuke Koya
Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes...
2016: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/27855634/identification-of-novel-targets-of-diabetic-nephropathy-and-pedf-peptide-treatment-using-rna-seq
#11
Ana Rubin, Anna C Salzberg, Yuka Imamura, Anzor Grivitishvilli, Joyce Tombran-Tink
BACKGROUND: Diabetic nephropathy (DN) is a major complication of type1 and type 2 diabetes. Understanding how diabetes regulate transcriptome dynamics in DN is important for understanding the biology of the disease and for guiding development of new treatments. RESULTS: We analyzed the kidney transcriptome of a DN mouse model, D2.B6-Ins2 (Akita) /MatbJ, before/after treatment with P78-PEDF. Age, weight, and gender-matched mice and wild-type (wt) littermates were treated at 6 weeks (early treatment) or 12 weeks (late treatment) of age for the duration of 6 weeks...
November 17, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27802520/inner-retinal-oxygen-delivery-metabolism-and-extraction-fraction-in-ins2akita-diabetic-mice
#12
Norman P Blair, Justin Wanek, Anthony E Felder, Katherine C Brewer, Charlotte E Joslin, Mahnaz Shahidi
Purpose: Retinal nonperfusion and hypoxia are important factors in human diabetic retinopathy, and these presumably inhibit energy production and lead to cell death. The purpose of this study was to elucidate the effect of diabetes on inner retinal oxygen delivery and metabolism in a mouse model of diabetes. Methods: Phosphorescence lifetime and blood flow imaging were performed in spontaneously diabetic Ins2Akita (n = 22) and nondiabetic (n = 22) mice at 12 and 24 weeks of age to measure retinal arterial (O2A) and venous (O2V) oxygen contents and total retinal blood flow (F)...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27797146/innovative-technologies-in-nanomedicines-from-passive-targeting-to-active-targeting-from-controlled-pharmacokinetics-to-controlled-intracellular-pharmacokinetics
#13
Yusuke Sato, Yu Sakurai, Kazuaki Kajimoto, Takashi Nakamura, Yuma Yamada, Hidetaka Akita, Hideyoshi Harashima
Nanomedicines promise to extend drug therapy from small molecular compounds to proteins/nucleic acids/genes. Multifunctional envelope-type nanodevices (MENDs) have been developed for delivering such molecules to the site of action. The YSK-MEND contains new types of pH-responsive cationic lipids to efficiently deliver siRNA to hepatocytes via receptor-mediated endocytosis and use in treating hepatitis C and B in model mice. The RGD ligand is introduced to target tumor endothelial cells (TEC) and RGD-MEND is able to send siRNA to TEC to regulate the function of tumor microenvironments...
October 31, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27665690/lymphangiogenesis-and-nos-localization-in-healing-process-after-tooth-extraction-in-akita-mouse
#14
Shinya Takahashi, Ryuta Kikuchi, Kimiharu Ambe, Toshihiro Nakagawa, Satoshi Takada, Takashi Ohno, Hiroki Watanabe
Type I diabetes, an autoimmune disease, induces insulin deficiency, which then disrupts vascular endothelial cell function, affecting blood and lymphatic vessels. Nitric oxide (NO) is an immune-induced destructive mediator in type I diabetes, and inhibition of its production promotes arteriosclerosis. In this study, lymphangiogenesis and expression of NO synthase (NOS) during the healing process after tooth extraction were investigated immunohistochemically in control (C57BL) and Akita mice as a diabetes model...
2016: Bulletin of Tokyo Dental College
https://www.readbyqxmd.com/read/27595114/experimental-diabetes-mellitus-in-different-animal-models
#15
REVIEW
Amin Al-Awar, Krisztina Kupai, Médea Veszelka, Gergő Szűcs, Zouhair Attieh, Zsolt Murlasits, Szilvia Török, Anikó Pósa, Csaba Varga
Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27581061/myostatin-inhibition-therapy-for-insulin-deficient-type-1-diabetes
#16
Samantha K Coleman, Irena A Rebalka, Donna M D'Souza, Namita Deodhare, Eric M Desjardins, Thomas J Hawke
While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27547413/dipeptidyl-peptidase-4-inhibition-by-saxagliptin-prevents-inflammation-and-renal-injury-by-targeting-the-nlrp3-asc-inflammasome
#17
Yochai Birnbaum, Mandeep Bajaj, Jinqiao Qian, Yumei Ye
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor activation delays the progression of diabetic nephropathy (DN) in rodents. The NOD-like receptor 3 (Nlrp3) inflammasome plays an important role in DN. Dipeptidyl peptidase-4 inhibitors (DPP4I) inhibit the degradation of endogenous GLP-1 and various other active substances. We assessed whether DPP4I attenuates diabetes-induced activation of the inflammasome and progression of DN in mice with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM)...
2016: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/27475229/stromal-cell-derived-factor-1-is-upregulated-by%C3%A2-dipeptidyl-peptidase-4-inhibition-and-has%C3%A2-protective-roles-in-progressive-diabetic%C3%A2-nephropathy
#18
Satoru Takashima, Hiroki Fujita, Hiromi Fujishima, Tatsunori Shimizu, Takehiro Sato, Tsukasa Morii, Katsushi Tsukiyama, Takuma Narita, Takamune Takahashi, Daniel J Drucker, Yutaka Seino, Yuichiro Yamada
The role of stromal cell-derived factor-1 (SDF-1) in the pathogenesis of diabetic nephropathy and its modification by dipeptidyl peptidase-4 (DPP-4) inhibition are uncertain. Therefore, we studied this independent of glucagon-like peptide-1 receptor (GLP-1R) signaling using two Akita diabetic mouse models, the diabetic-resistant C57BL/6-Akita and diabetic-prone KK/Ta-Akita. Increased SDF-1 expression was found in glomerular podocytes and distal nephrons in the diabetic-prone mice, but not in kidneys from diabetic-resistant mice...
October 2016: Kidney International
https://www.readbyqxmd.com/read/27440994/glut1-activity-contributes-to-the-impairment-of-pedf-secretion-by-the-rpe
#19
Sofia M Calado, Liliana S Alves, Sónia Simão, Gabriela A Silva
PURPOSE: In this study, we aimed to understand whether glucose transporter 1 (GLUT1) activity affects the secretion capacity of antiangiogenic factor pigment epithelium-derived factor (PEDF) by the RPE cells, thus explaining the reduction in PEDF levels observed in patients with diabetic retinopathy (DR). METHODS: Analysis of GLUT1 expression, localization, and function was performed in vitro in RPE cells (D407) cultured with different glucose concentrations, corresponding to non-diabetic (5 mM of glucose) and diabetic (25 mM of glucose) conditions, further subjected to normoxia or hypoxia...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27388219/nmda-receptors-as-potential-therapeutic-targets-in-diabetic-nephropathy-increased-renal-nmda-receptor-subunit-expression-in-akita-mice-and-reduced-nephropathy-following-sustained-treatment-with-memantine-or-mk-801
#20
Hila Roshanravan, Eun Young Kim, Stuart E Dryer
N-methyl-d-aspartate (NMDA) receptors are expressed throughout the kidney, and the abundance of these receptors and some of their endogenous agonists are increased in diabetes. Moreover, sustained activation of podocyte NMDA receptors induces Ca(2+) influx, oxidative stress, loss of slit diaphragm proteins, and apoptosis. We observed that NMDA receptor subunits and their transcripts are increased in podocytes and mesangial cells cultured in elevated glucose compared with controls. A similar increase in NMDA subunits, especially NR1, NR2A, and NR2C, was observed in glomeruli and tubules of Akita mice...
October 2016: Diabetes
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