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https://www.readbyqxmd.com/read/27909574/characterization-of-5-2-18-f-fluoroethoxy-l-tryptophan-for-pet-imaging-of-the-pancreas
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27382987/increase-of-total-nephron-albumin-filtration-and-reabsorption-in-diabetic-nephropathy
#13
Keita P Mori, Hideki Yokoi, Masato Kasahara, Hirotaka Imamaki, Akira Ishii, Takashige Kuwabara, Kenichi Koga, Yukiko Kato, Naohiro Toda, Shoko Ohno, Koichiro Kuwahara, Tomomi Endo, Kazuwa Nakao, Motoko Yanagita, Masashi Mukoyama, Kiyoshi Mori
The amount of albumin filtered through the glomeruli and reabsorbed at the proximal tubules in normal and in diabetic kidneys is debated. The megalin/cubilin complex mediates protein reabsorption, but genetic knockout of megalin is perinatally lethal. To overcome current technical problems, we generated a drug-inducible megalin-knockout mouse line, megalin(lox/lox);Ndrg1-CreER(T2) (iMegKO), in which megalin expression can be shut off at any time by administration of tamoxifen (Tam). Tam administration in adult iMegKO mice decreased the expression of renal megalin protein by 92% compared with that in wild-type C57BL/6J mice and almost completely abrogated renal reabsorption of intravenously injected retinol-binding protein...
July 6, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27376728/lactobacillus-salivarius-reverse-diabetes-induced-intestinal-defense-impairment-in-mice-through-non-defensin-protein
#14
Pei-Hsuan Chung, Ying-Ying Wu, Pei-Hsuan Chen, Chang-Phone Fung, Ching-Mei Hsu, Lee-Wei Chen
Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated...
September 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27335233/decreased-satellite-cell-number-and-function-in-humans-and-mice-with-type-1-diabetes-is-the-result-of-altered-notch-signaling
#15
Donna M D'Souza, Sarah Zhou, Irena A Rebalka, Blair MacDonald, Jasmin Moradi, Matthew P Krause, Dhuha Al-Sajee, Zubin Punthakee, Mark A Tarnopolsky, Thomas J Hawke
Type 1 diabetes (T1D) negatively influences skeletal muscle health; however, its effect on muscle satellite cells (SCs) remains largely unknown. SCs from samples from rodents (Akita) and human subjects with T1D were examined to discern differences in SC density and functionality compared with samples from their respective control subjects. Examination of the Notch pathway was undertaken to investigate its role in changes to SC functionality. Compared with controls, Akita mice demonstrated increased muscle damage after eccentric exercise along with a decline in SC density and myogenic capacity...
October 2016: Diabetes
https://www.readbyqxmd.com/read/27297781/nanoparticle-mediated-mir200-b-delivery-for-the-treatment-of-diabetic-retinopathy
#16
Rajendra Narayan Mitra, Chance A Nichols, Junjing Guo, Rasha Makkia, Mark J Cooper, Muna I Naash, Zongchao Han
We recently reported that the Ins2(Akita) mouse is a good model for late-onset diabetic retinopathy. Here, we investigated the effect of miR200-b, a potential anti-angiogenic factor, on VEGF receptor 2 (VEGFR-2) expression and to determine the underlying angiogenic response in mouse endothelial cells, and in retinas from aged Ins2(Akita) mice. MiR200-b and its native flanking sequences were amplified and cloned into a pCAG-eGFP vector directed by the ubiquitous CAG promoter (namely pCAG-miR200-b-IRES-eGFP)...
August 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27231121/effect-of-particle-size-on-their-accumulation-in-an-inflammatory-lesion-in-a-dextran-sulfate-sodium-dss-induced-colitis-model
#17
Ayaka Watanabe, Hiroki Tanaka, Yu Sakurai, Kota Tange, Yuta Nakai, Tatsuya Ohkawara, Hiroshi Takeda, Hideyoshi Harashima, Hidetaka Akita
Taking advantage of the enhanced permeation and retention (EPR) effect is a promising approach for delivering macromolecules or nanoparticles to tumors. Recent studies revealed that this strategy is also applicable for targeting other pathological lesions (i.e. inflammatory disease). In the present study, we report the optimal size of a nanoparticle for allowing the higher accumulation of a particle in an inflammatory lesion using a dextran sulfate sodium (DSS)-induced colitis model. As a nanoparticle platform, we utilized a SS-cleavable and pH-activated lipid-like material (ssPalm), that can be used to produce particles in a variety of sizes ranging from 50nm to 180nm while using the same lipid composition...
July 25, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27186534/quantitative-assessment-of-retinopathy-using-multi-parameter-image-analysis
#18
Zahra Ghanian, Kevin Staniszewski, Nasim Jamali, Reyhaneh Sepehr, Shoujian Wang, Christine M Sorenson, Nader Sheibani, Mahsa Ranji
A multi-parameter quantification method was implemented to quantify retinal vascular injuries in microscopic images of clinically relevant eye diseases. This method was applied to wholemount retinal trypsin digest images of diabetic Akita/+, and bcl-2 knocked out mice models. Five unique features of retinal vasculature were extracted to monitor early structural changes and retinopathy, as well as quantifying the disease progression. Our approach was validated through simulations of retinal images. Results showed fewer number of cells (P = 5...
April 2016: Journal of Medical Signals and Sensors
https://www.readbyqxmd.com/read/27150147/pulmonary-administration-of-gw0742-a-high-affinity-peroxisome-proliferator-activated-receptor-agonist-repairs-collapsed-alveoli-in-an-elastase-induced-mouse-model-of-emphysema
#19
Chihiro Ozawa, Michiko Horiguchi, Tomomi Akita, Yuki Oiso, Kaori Abe, Tomoki Motomura, Chikamasa Yamashita
Pulmonary emphysema is a disease in which lung alveoli are irreversibly damaged, thus compromising lung function. Our previous study revealed that all-trans-retinoic acid (ATRA) induces the differentiation of human lung alveolar epithelial type 2 progenitor cells and repairs the alveoli of emphysema model mice. ATRA also reportedly has the ability to activate peroxisome proliferator-activated receptor (PPAR) β/δ. A selective PPARβ/δ ligand has been reported to induce the differentiation of human keratinocytes during wound repair...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27148685/distal-retinal-ganglion-cell-axon-transport-loss-and-activation-of-p38-mapk-stress-pathway-following-vegf-a-antagonism
#20
R Foxton, A Osborne, K R Martin, Y-S Ng, D T Shima
There is increasing evidence that VEGF-A antagonists may be detrimental to neuronal health following ocular administration. Here we investigated firstly the effects of VEGF-A neutralization on retinal neuronal survival in the Ins2(Akita) diabetic and JR5558 spontaneous choroidal neovascularization (CNV) mice, and then looked at potential mechanisms contributing to cell death. We detected elevated apoptosis in the ganglion cell layer in both these models following VEGF-A antagonism, indicating that even when vascular pathologies respond to treatment, neurons are still vulnerable to reduced VEGF-A levels...
2016: Cell Death & Disease
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