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Akita mice

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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Priyanka Prathipati, Naira Metreveli, Shyam Sundar Nandi, Suresh C Tyagi, Paras K Mishra
Elevated expression and activity of matrix metalloproteinase-9 (MMP9) and decreased contractility of cardiomyocytes are documented in diabetic hearts. However, it is unclear whether MMP is involved in the regulation of contractility of cardiomyocytes in diabetic hearts. In the present study, we tested the hypothesis that MMP9 regulates contractility of cardiomyocytes in diabetic hearts, and ablation of MMP9 prevents impaired contractility of cardiomyocytes in diabetic hearts. To determine the specific role of MMP9 in cardiomyocyte contractility, we used 12-14 week male WT (normoglycemic sibling of Akita), Akita, and Ins(2+∕-)/MMP9(-∕-) (DKO) mice...
2016: Frontiers in Physiology
Koji Akita, Kikuo Isoda, Yayoi Okabayasi, Kazunori Shimada, Hiroyuki Daida
No abstract text is available yet for this article.
May 15, 2016: International Journal of Cardiology
Yasuhiro Kazuki, Masaharu Akita, Kaoru Kobayashi, Mitsuhiko Osaki, Daisuke Satoh, Ryo Ohta, Satoshi Abe, Shoko Takehara, Kanako Kazuki, Hiroshi Yamazaki, Tetsuya Kamataki, Mitsuo Oshimura
Thalidomide is a teratogen in humans but not in rodents. It causes multiple birth defects including malformations of limbs, ears, and other organs. However, the species-specific mechanism of thalidomide teratogenicity is not completely understood. Reproduction of the human teratogenicity of thalidomide in rodents has previously failed because of the lack of a model reflecting human drug metabolism. In addition, because the maternal metabolic effect cannot be eliminated, the migration of unchanged thalidomide to embryos is suppressed, and the metabolic activation is insufficient to develop teratogenicity...
2016: Scientific Reports
Catherine K Hathaway, Albert S Chang, Ruriko Grant, Hyung-Suk Kim, Victoria J Madden, C Robert Bagnell, J Charles Jennette, Oliver Smithies, Masao Kakoki
Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2(Akita) gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal...
February 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
Rosalinda Madonna, Gaia Giovannelli, Pamela Confalone, Francesca Vera Renna, Yong-Jian Geng, Raffaele De Caterina
BACKGROUND: We tested the hypothesis that glucose-induced hyperosmolarity, occurring in diabetic hyperglycemia, promotes retinal angiogenesis, and that interference with osmolarity signaling ameliorates excessive angiogenesis and retinopathy in vitro and in vivo. METHODS AND RESULTS: We incubated human aortic (HAECs) and dermal microvascular endothelial cells (HMVECs) with glucose or mannitol for 24 h and tested them for protein levels and in vitro angiogenesis...
2016: Cardiovascular Diabetology
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