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https://www.readbyqxmd.com/read/28607540/effects-of-high-fat-feeding-on-skeletal-muscle-gene-expression-in-diabetic-goto-kakizaki-rats
#1
Jing Nie, Debra C DuBois, Bai Xue, William J Jusko, Richard R Almon
In the present report, we examined the responses of diabetic Goto-Kakizaki (GK) rats and control Wistar-Kyoto (WKY) rats fed either a standard chow or high-fat diet (HFD) from weaning to 20 weeks of age. This comparison included gene expression profiling of skeletal muscle using Affymetrix gene array chips. The expression profiling is interpreted within the context of a wide array of physiological measurements. Genes whose expressions are different between the 2 strains regardless of diet, as well as genes that differ between strains only with HFD, were identified...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28596492/detection-of-tumor-derived-dna-dispersed-in-the-airway-improves-the-diagnostic-accuracy-of-bronchoscopy-for-lung-cancer
#2
Taichiro Goto, Yosuke Hirotsu, Takahiro Nakagomi, Daichi Shikata, Yujiro Yokoyama, Kenji Amemiya, Toshiharu Tsutsui, Yumiko Kakizaki, Toshio Oyama, Hitoshi Mochizuki, Yoshihiro Miyashita, Masao Omata
The diagnostic accuracy of bronchoscopy for detecting lung cancer, especially peripheral lung cancer with lesions outside the endoscopically visible range, remains unsatisfactory. The aim of this study was to perform next-generation sequencing on bronchoscopic specimens to determine whether this improves the accuracy of bronchoscopy for diagnosing lung cancer and to identify factors influencing sensitivity. The bronchoscopic sensitivity for diagnosing lung cancer was initially evaluated in 191 patients who underwent lobectomy after bronchoscopy at our hospital...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28573460/brain-glp-1-igf-1-signaling-and-autophagy-mediate-exendin-4-protection-against-apoptosis-in-type-2-diabetic-rats
#3
Emanuel Candeias, Inês Sebastião, Susana Cardoso, Cristina Carvalho, Maria Sancha Santos, Catarina Resende Oliveira, Paula I Moreira, Ana I Duarte
Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD). Since impaired brain insulin signaling may constitute the crosslink between T2D and AD, its restoration may be potentially therapeutic herein. Accordingly, the insulinotropic anti-T2D drugs from glucagon-like peptide-1 (GLP-1) mimetics, namely, exendin-4 (Ex-4), could be a promising therapy...
June 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28570978/inhibition-of-long-noncoding-rna-igf2as-promotes-angiogenesis-in-type-2-diabetes
#4
Zhuo Zhao, Bin Liu, Bo Li, Chunli Song, Hongying Diao, Ziyuan Guo, Zhibo Li, Jichang Zhang
BACKGROUND: In this study, the angiogenic effect of long noncoding RNA (lncRNA), insulin growth factor 2 antisense (IGF2AS) in type 2 diabetes was evaluated. METHODS: Between Wistar rat and Goto-Kakizaki (GK) rat, a genetic model of type 2 diabetes, mRNA expressions of IGF2AS and IGF2 in myocardial microvascular endothelial (mMVE) cells were compared by qRT-PCR. In GK mMVE cells, IGF2AS was inhibited by siRNA. Its effects on cell proliferation and invasion were evaluated by MTT and wound-healing assays...
May 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28559245/temporal-transcriptomic-and-proteomic-landscapes-of-deteriorating-pancreatic-islets-in-type-2-diabetic-rats
#5
Junjie Hou, Zonghong Li, Wen Zhong, Qiang Hao, Lei Lei, Linlin Wang, Dongyu Zhao, Pingyong Xu, Yifa Zhou, You Wang, Tao Xu
Progressive reduction in β-cell mass and function comprise the core of the pathogenesis mechanism of type 2 diabetes (T2D). The process of deteriorating pancreatic islets, in which a complex network of molecular events was involved, is not yet fully characterized. Here we employed RNA Sequencing and tandem mass tag (TMT) based quantitative proteomics technology to measure the temporal mRNA and protein expression changes of pancreatic islets in Goto-Kakizaki (GK) rats from 4 to 24 weeks of age. Our omics dataset outlined the dynamics of molecular network during the deterioration of GK islets as two stages: the early stage (4-6 weeks) is characterized by anaerobic glycolysis, inflammation priming, and compensation for insulin synthesis, whereas the late stage (8-24 weeks) is characterized by inflammation amplification and compensation failure...
May 30, 2017: Diabetes
https://www.readbyqxmd.com/read/28547133/hsf1-acetylation-decreases-its-transcriptional-activity-and-enhances-glucolipotoxicity-induced-apoptosis-in-rat-and-human-beta-cells
#6
Indri Purwana, Jun J Liu, Bernard Portha, Jean Buteau
AIMS/HYPOTHESIS: Heat shock factor protein 1 (HSF1) is a transcription factor that regulates the expression of key molecular chaperones, thereby orchestrating the cellular response to stress. This system was recently implicated in the control of insulin sensitivity and is therefore being scrutinised as a novel therapeutic avenue for type 2 diabetes. However, the regulation and biological actions of HSF1 in beta cells remain elusive. Herein, we sought to investigate the regulation of HSF1 in pancreatic beta cells and to study its potential role in cell survival...
May 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28542610/gpr40-partial-agonist-mk-2305-lower-fasting-glucose-in-the-goto-kakizaki-rat-via-suppression-of-endogenous-glucose-production
#7
Corin Miller, Michele J Pachanski, Melissa E Kirkland, Daniel T Kosinski, Joel Mane, Michelle Bunzel, Jin Cao, Sarah Souza, Brande Thomas-Fowlkes, Jerry Di Salvo, Adam B Weinglass, Xiaoyan Li, Robert W Myers, Kevin Knagge, Paul E Carrington, William K Hagmann, Maria E Trujillo
GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40 partial agonists improve glucose homeostasis, we evaluated the effects of MK-2305, a potent and selective partial GPR40 agonist, in diabetic Goto Kakizaki rats. MK-2305 decreased fasting glucose after acute and chronic treatment. MK-2305-mediated changes in glucose were coupled with increases in plasma insulin during hyperglycemia and glucose challenges but not during fasting, when glucose was normalized...
2017: PloS One
https://www.readbyqxmd.com/read/28541489/respiratory-effects-and-systemic-stress-response-following-acute-acrolein-inhalation-in-rats
#8
Samantha J Snow, Marie A McGee, Andres Henriquez, Judy E Richards, Mette C Schladweiler, Allen D Ledbetter, Urmila P Kodavanti
Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically-impaired models. We examined respiratory and systemic effects following exposure to a sensory irritant acrolein to elucidate the systemic and pulmonary consequences in healthy and diabetic rat models. Male Wistar and Goto Kakizaki (GK) rats, a non-obese type II diabetic Wistar-derived model, were exposed by inhalation to 0, 2, or 4 ppm acrolein, 4h/day for 1 or 2 days...
May 24, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28458353/the-sodium-glucose-cotransporter-2-inhibitor-ipragliflozin-promotes-preferential-loss-of-fat-mass-in-non-obese-diabetic-goto-kakizaki-rats
#9
Toshiyuki Takasu, Yuka Hayashizaki, Jiro Hirosumi, Hideaki Minoura, Nobuaki Amino, Eiji Kurosaki, Shoji Takakura
Sodium glucose cotransporter 2 (SGLT2) inhibitors improve hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. In addition to their antihyperglycemic effect, SGLT2 inhibitors also reduce body weight and fat mass in obese and overweight patients with T2DM. However, whether or not SGLT2 inhibitors similarly affect body composition of non-obese patients with T2DM remains unclear. In this study, we investigated the effect of the SGLT2 inhibitor ipragliflozin on body composition in a Goto-Kakizaki (GK) rat model of non-obese T2DM...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28441970/salidroside-contributes-to-reducing-blood-pressure-and-alleviating-cerebrovascular-contractile-activity-in-diabetic-goto-kakizaki-rats-by-inhibition-of-l-type-calcium-channel-in-smooth-muscle-cells
#10
Yu-Guang Ma, Jun-Wei Wang, Yun-Gang Bai, Mei Liu, Man-Jiang Xie, Zhi-Jun Dai
BACKGROUND: Vascular disease is a common and often severe complication in diabetes mellitus. Hyperglycemia and hypertension are considered to be two of the leading risk factors for vascular complications in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetic patients at the same time. Salidroside (SAL) is the major active ingredient derived from Rhodiola. Recently, it has been reported that SAL have an obvious hypoglycemic effect in diabetes and show a beneficial activity in diabetic vascular dysfunction...
April 26, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28360538/antidiabetic-and-gastric-emptying-inhibitory-effect-of-herbal-melia-azedarach-leaf-extract-in-rodent-models-of-diabetes-type-2-mellitus
#11
Daniel Seifu, Lars E Gustafsson, Rajinder Chawla, Solomon Genet, Asfaw Debella, Mikael Holst, Per M Hellström
Diabetes type 2 is associated with impaired insulin production and increased insulin resistance. Treatment with antidiabetic drugs and insulin strives for normalizing glucose homeostasis. In Ethiopian traditional medicine, plant extracts of Melia azedarach are used to control diabetes mellitus and various gastrointestinal disorders. The objective of this study was to clarify the antidiabetic effects of M. azedarach leaf extracts in diabetic type 2 experimental animals. In this study, mice were injected with Melia extract intraperitoneally...
2017: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/28348018/synergistic-interaction-of-hypertension-and-diabetes-in-promoting-kidney-injury-and-the-role-of-endoplasmic-reticulum-stress
#12
Zhen Wang, Jussara M do Carmo, Nicola Aberdein, Xinchun Zhou, Jan M Williams, Alexandre A da Silva, John E Hall
Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively...
May 2017: Hypertension
https://www.readbyqxmd.com/read/28332581/elevated-mir-130a-mir130b-mir-152-expression-reduces-intracellular-atp-levels-in-the-pancreatic-beta-cell
#13
Jones K Ofori, Vishal A Salunkhe, Annika Bagge, Neelanjan Vishnu, Mototsugu Nagao, Hindrik Mulder, Claes B Wollheim, Lena Eliasson, Jonathan L S Esguerra
MicroRNAs have emerged as important players of gene regulation with significant impact in diverse disease processes. In type-2 diabetes, in which impaired insulin secretion is a major factor in disease progression, dysregulated microRNA expression in the insulin-secreting pancreatic beta cell has been widely-implicated. Here, we show that miR-130a-3p, miR-130b-3p, and miR-152-3p levels are elevated in the pancreatic islets of hyperglycaemic donors, corroborating previous findings about their upregulation in the islets of type-2 diabetes model Goto-Kakizaki rats...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315330/microrna-29-regulates-myocardial-microvascular-endothelial-cells-proliferation-and-migration-in-association-with-igf1-in-type-2-diabetes
#14
Zhenjie Li, Runxia Jiang, Qingcai Yue, Haiying Peng
BACKGROUND: In our study, we investigated the expression and function of microRNA-29 in myocardial microvascular endothelial cells (MMEVC) in type 2 diabetic Goto-Kakizaki (GK) rats. METHODS: MiR-29 gene expression was compared, by qRT-PCR between diabetic GK rat MMEVC and non-diabetic Wistar rat MMEVC. MiR-29 was downregulated in GK MMEVC and its effect on angiogenic properties of proliferation and migration was examined. Potential downstream target gene of miR-29, insulin growth factor 1 (IGF1), was assessed by dual-luciferase reporter assay, qRT-PCR and western blot in GK MMEVC...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28299342/relationship-between-immunological-abnormalities-in-rat-models-of-diabetes-mellitus-and-the-amplification-circuits-for-diabetes
#15
REVIEW
Yuji Takeda, Tomoko Shimomura, Hironobu Asao, Ichiro Wakabayashi
A better understanding of pathogenic mechanisms is required in order to treat diseases. However, the mechanisms of diabetes mellitus and diabetic complications are extremely complex. Immune reactions are involved in the pathogenesis of diabetes and its complications, while diabetes influences immune reactions. Furthermore, both diabetes and immune reactions are influenced by genetic and environmental factors. To address these issues, animal models are useful tools. So far, various animal models of diabetes have been developed in rats, which have advantages over mice models in terms of the larger volume of tissue samples and the variety of type 2 diabetes models...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28275538/analysis-of-significantly-mutated-genes-as-a-clinical-tool-for-the-diagnosis-in-a-case-of-lung-cancer
#16
Yoshihiro Miyashita, Yosuke Hirotsu, Toshiharu Tsutsui, Seishi Higashi, Yusuke Sogami, Yumiko Kakizaki, Taichiro Goto, Kenji Amemiya, Toshio Oyama, Masao Omata
Bronchoendoscopic examination is not necessarily comfortable procedure and limited by its sensitivity, depending on the location and size of the tumor lesion. Patients with a non-diagnostic bronchoendoscopic examination often undergo further invasive examinations. Non-invasive diagnostic tool of lung cancer is desired. A 72-year-old man had a 3.0 cm × 2.5 cm mass lesion in the segment B1 of right lung. Cytological examination of sputum, bronchial washing and curetted samples were all "negative". We could confirm a diagnosis of lung cancer after right upper lung lobe resection pathologically, and also obtained concordant results by genomic analysis using cytological negative samples from airways collected before operation...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28214972/avocado-oil-induces-long-term-alleviation-of-oxidative-damage-in-kidney-mitochondria-from-type-2-diabetic-rats-by-improving-glutathione-status
#17
Omar Ortiz-Avila, María Del Consuelo Figueroa-García, Claudia Isabel García-Berumen, Elizabeth Calderón-Cortés, Jorge A Mejía-Barajas, Alain R Rodriguez-Orozco, Ricardo Mejía-Zepeda, Alfredo Saavedra-Molina, Christian Cortés-Rojo
Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion...
February 18, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28207836/tmg-123-a-novel-glucokinase-activator-exerts-durable-effects-on-hyperglycemia-without-increasing-triglyceride-in-diabetic-animal-models
#18
Yoshinori Tsumura, Yu Tsushima, Azusa Tamura, Makiko Hasebe, Masanobu Kanou, Hirotsugu Kato, Tsunefumi Kobayashi
Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues...
2017: PloS One
https://www.readbyqxmd.com/read/28197316/design-and-synthesis-of-novel-selective-gpr40-agopams
#19
Christopher W Plummer, Matthew J Clements, Helen Chen, Murali Rajagopalan, Hubert Josien, William K Hagmann, Michael Miller, Maria E Trujillo, Melissa Kirkland, Daniel Kosinski, Joel Mane, Michele Pachanski, Boonlert Cheewatrakoolpong, Andrew F Nolting, Robert Orr, Melodie Christensen, Louis-Charles Campeau, Michael J Wright, Randal Bugianesi, Sarah Souza, Xiaoping Zhang, Jerry Di Salvo, Adam B Weinglass, Richard Tschirret-Guth, Ravi Nargund, Andrew D Howard, Steven L Colletti
GPR40 is a G-protein-coupled receptor expressed primarily in pancreatic islets and intestinal L-cells that has been a target of significant recent therapeutic interest for type II diabetes. Activation of GPR40 by partial agonists elicits insulin secretion only in the presence of elevated blood glucose levels, minimizing the risk of hypoglycemia. GPR40 agoPAMs have shown superior efficacy to partial agonists as assessed in a glucose tolerability test (GTT). Herein, we report the discovery and optimization of a series of potent, selective GPR40 agoPAMs...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28163042/munc18b-increases-insulin-granule-fusion-restoring-deficient-insulin-secretion-in-type-2-diabetes-human-and-goto-kakizaki-rat-islets-with-improvement-in-glucose-homeostasis
#20
Tairan Qin, Tao Liang, Dan Zhu, Youhou Kang, Li Xie, Subhankar Dolai, Shuzo Sugita, Noriko Takahashi, Claes-Goran Ostenson, Kate Banks, Herbert Y Gaisano
Reduced pancreatic islet levels of Munc18a/SNARE complex proteins have been postulated to contribute to the deficient glucose-stimulated insulin secretion (GSIS) in type-2 diabetes (T2D). Whereas much previous work has purported Munc18a/SNARE complex (Syntaxin-1A/VAMP-2/SNAP25) to be primarily involved in predocked secretory granule (SG) fusion, less is known about newcomer SGs that undergo minimal docking time at the plasma membrane before fusion. Newcomer SG fusion has been postulated to involve a distinct SM/SNARE complex (Munc18b/Syntaxin-3/VAMP8/SNAP25), whose levels we find also reduced in islets of T2D humans and T2D Goto-Kakizaki (GK) rats...
February 2017: EBioMedicine
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