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Goto kakizaki

Kenji Sugawara, Kohei Honda, Yoshie Reien, Norihide Yokoi, Chihiro Seki, Harumi Takahashi, Kohtaro Minami, Ichiro Mori, Akio Matsumoto, Haruaki Nakaya, Susumu Seino
Insulin secretagogues are used for treatment of type 2 diabetes. We attempted to discover novel small molecules to stimulate insulin secretion by using in silico similarity search using sulfonylureas as query, followed by measurement of insulin secretion. Among 38 compounds selected by in silico similarity search, we found three diphenylsemicarbazides and one quinolone that stimulate insulin secretion. We focused on compound 8 (C8), which had the strongest insulin-secreting effect. Based on the structure-activity relationship of C8-derivatives, we identified diphenylthiosemicarbazide (DSC) 108 as the most potent secretagogue...
2016: PloS One
Masatoshi Kubota, Reiko Watanabe, Miki Yamaguchi, Michihiro Hosojima, Akihiko Saito, Mikio Fujii, Shinobu Fujimura, Motoni Kadowaki
We previously reported that rice endosperm protein (REP) has renoprotective effects in Goto-Kakizaki rats, a non-obese diabetic model. However, whether these effects occur in obese diabetes remains unclear. This study aimed to clarify the effects of REP on obese diabetes, especially on fatty liver and diabetic nephropathy, using the obese diabetic model Zucker diabetic fatty (ZDF) rats. In total, 7-week-old male ZDF rats were fed diets containing 20 % REP or casein (C) for 8 weeks. Changes in fasting blood glucose levels and urinary markers were monitored during the experimental period...
October 11, 2016: British Journal of Nutrition
Talma Rosenthal, Firas Younis, Ariela Alter
Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD), and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH) rats...
March 26, 2010: Pharmaceuticals
Yuhuan Meng, Yujia Guan, Wenlu Zhang, Yu-E Wu, Huanhuan Jia, Yu Zhang, Xiuqing Zhang, Hongli Du, Xiaoning Wang
The Goto-Kakizaki (GK) rat is an animal model of non-obese type 2 diabetes (T2D). The GK rat was generated through the introduction of various genetic mutations from continuous inbreeding; these rats develop diabetes spontaneously. The mutated genes in GK rats may play key roles in the regulation of diabetes. The hypothalamus plays a central role in systematic energy homeostasis. Here, the hypothalamic transcriptomes in GK and Wistar rats at 4, 8 and 12 weeks were investigated by RNA-seq, and multiple variants and gene expression profiles were obtained...
September 28, 2016: Scientific Reports
Jazyra Zynat, Yuyu Guo, Yingli Lu, Dongping Lin
Objectives. This study aimed to explore the expression of GLP-1 receptor in hypothalamus and gastrointestinal tissues after Roux-en-Y gastric bypass (RYGB) surgery in diabetic rats. Methods. Male 12-week-old Wistar rats (control) and Goto-Kakizaki rats (diabetic) were randomly divided into two groups, respectively: control sham surgery group (C), control RYGB group (C + R), diabetic sham surgery group (D), and diabetic RYGB group (D + R). Body weight and blood glucose were monitored before and after surgery every week...
2016: International Journal of Endocrinology
Pamela J Kaisaki, Georg W Otto, Karène Argoud, Stephan C Collins, Robert H Wallis, Steven P Wilder, Anthony C Y Yau, Christophe Hue, Sophie Calderari, Marie-Thérèse Bihoreau, Jean-Baptiste Cazier, Richard Mott, Dominique Gauguier
To test the impact of genetic heterogeneity on cis- and trans-mediated mechanisms of gene expression regulation, we profiled the transcriptome of adipose tissue in 20 inbred congenic strains derived from diabetic Goto-Kakizaki (GK) rats and Brown-Norway (BN) controls, which contain well-defined blocks (1Mb-183Mb) of genetic polymorphisms, and in 123 genetically heterogeneous rats of an (GKxBN)F2 offspring. Within each congenic we identified 73 to 1,351 differentially expressed genes (DEG), only 7.7% of which mapped within the congenic blocks, and which may be regulated in cis The remainder localised outside the blocks, and therefore must be regulated in trans Most trans-regulated genes exhibited approximately two-fold expression changes, consistent with mono-allelic expression...
September 19, 2016: G3: Genes—Genomes—Genetics
Jing Zhang, Mai Shirai, Ryuji Yamamoto, Yasuo Yamakoshi, Shinichiro Oida, Chikahiro Ohkubo, Jianyu Zeng
PURPOSE: Compared with the general population, a poorer quality of bone-implant osseointegration occurs and at a higher failure rate in patients with type 2 diabetes mellitus. The aim of this study was to analyze the effects of local injection of nerve growth factor at the bone-implant interface after implantation in type 2 diabetic rats. MATERIALS AND METHODS: Goto-Kakizaki (GK) rats (n = 30) were used as a model of type 2 diabetes mellitus, and Wistar rats were used as a control (n = 15)...
September 2016: International Journal of Oral & Maxillofacial Implants
Harilal Patel, Poonam Giri, Nuggehally R Srinivas
Goto-Kakizaki (GK) rats represent a unique non-obese and lean model with manifestation of type 2 diabetes (T2DM) broadly mimicking the human T2DM development. Therefore, in addition to the use of GK rats to test the efficacy of drugs, it may represent a great tool to study the influence of altered physiological process and/or organ specific pathophysiological changes (i.e., liver, kidney, etc.) on the disposition of drugs. The objectives of the review were: (a) to compile the published pharmacokinetic data of several drugs, such as cephalexin, cyclosporine, exendin-4, gliclazide, grepafloxacin, rosuvastatin, salsalate, salicylic acid, and theophylline, in GK rats relative to normal rats; and (b) critically evaluate the possible role of physiologically altered processes on the pharmacokinetics of reviewed drugs...
September 13, 2016: European Journal of Drug Metabolism and Pharmacokinetics
Yin Lin, Kasper Krogh-Andersen, Julien Pelletier, Harold Marcotte, Claes-Göran Östenson, Lennart Hammarström
Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by intestinal cells and stimulates insulin secretion from the pancreas in a glucose-dependent manner. Exogenously supplied GLP-1 analogues are used in the treatment of type 2 diabetes. An anti-diabetic effect of Lactobacillus in lowering plasma glucose levels and its use as a vehicle for delivery of protein and antibody fragments has been shown previously. The aim of this study was to employ lactobacilli as a vehicle for in situ production and delivery of GLP-1 analogue to normalize blood glucose level in diabetic GK (Goto-Kakizaki) rats...
2016: PloS One
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
Shangeng Weng, Bin Zhang, Changguo Xu, Su Feng, Hongxing He
BACKGROUND: This study aimed to investigate the influence of new biliopancreatic diversion (NBPD) and duodenal-jejunal bypass (DJB) surgery on blood glucose, lipids, gastrointestinal hormones, and insulin in Goto-Kakizaki (GK) rats, an animal model for type 2 diabetes, in order to elucidate the mechanisms underlying the therapeutic effect of these types of surgery on this clinical condition. METHODS: Thirty 30 male GK rats (SPF) aged 12 weeks were randomly assigned into three groups (n = 10 per group): sham group, NBPD group, and DJB group...
August 15, 2016: Obesity Surgery
Sevil Korkmaz-Icöz, Alice Lehner, Shiliang Li, Adrian Vater, Tamás Radovits, Maik Brune, Mihály Ruppert, Xiaoxin Sun, Paige Brlecic, Markus Zorn, Matthias Karck, Gábor Szabó
The Goto-Kakizaki (GK) rat, a non-obese model of type 2 diabetes mellitus (T2DM), was generated by the selective inbreeding of glucose-intolerant Wistar rats. This is a convenient model for studying diabetes-induced cardiomyopathy independently from the effects of the metabolic syndrome. We investigated the myocardial functional and structural changes and underlying molecular pathomechanisms of short-term and mild T2DM. The presence of DM was confirmed by an impaired oral glucose tolerance in the GK rats compared with the age-matched nondiabetic Wistar rats...
October 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Yuchi Liu, Xunbai Mei, Jielei Li, Nicola Lai, Xin Yu
The study aims to characterize age-associated changes in skeletal muscle bioenergetics by evaluating the response to ischemia-reperfusion in the skeletal muscle of the Goto-Kakizaki (GK) rats, a rat model of non-obese type 2 diabetes (T2D). (31)P magnetic resonance spectroscopy (MRS) and blood oxygen level-dependent (BOLD) MRI was performed on the hindlimb of young (12 weeks) and adult (20 weeks) GK and Wistar (control) rats. (31)P-MRS and BOLD-MRI data were acquired continuously during an ischemia and reperfusion protocol to quantify changes in phosphate metabolites and muscle oxygenation...
August 2016: Physiological Reports
Hanna K E Frost, Akira Kodama, Per Ekström, Lars B Dahlin
Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug candidate for improving the outcome after peripheral nerve injuries. We raised the question if exogenous G-CSF can improve nerve regeneration following a clinically relevant model - nerve transection and repair - in healthy and diabetic rats. In short-term experiments, distance of axonal regeneration and extent of injury-induced Schwann cell death was quantified by staining for neurofilaments and cleaved caspase 3, respectively, seven days after repair...
August 4, 2016: Neuroscience
Márta Sárközy, Gergő Szűcs, Veronika Fekete, Márton Pipicz, Katalin Éder, Renáta Gáspár, Andrea Sója, Judit Pipis, Péter Ferdinandy, Csaba Csonka, Tamás Csont
BACKGROUND: There is a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM) due to the worldwide obesity epidemic. However, a significant proportion of T2DM patients are non-obese and they also have an increased risk of cardiovascular diseases. As the Goto-Kakizaki (GK) rat is a well-known model of non-obese T2DM, the goal of this study was to investigate the effect of non-obese T2DM on cardiac alterations of the transcriptome in GK rats. METHODS: Fasting blood glucose, serum insulin and cholesterol levels were measured at 7, 11, and 15 weeks of age in male GK and control rats...
2016: Cardiovascular Diabetology
Yuki Matsunaga, Takayuki Negishi, Akinori Hatakeyama, Yuta Kawagoe, Erika Sawano, Tomoko Tashiro
Insulin receptor signaling has been shown to regulate essential aspects of CNS function such as synaptic plasticity and neuronal survival. To elucidate its roles during CNS development in vivo, we examined the synaptic and cognitive development of the spontaneously diabetic Goto-Kakizaki (GK) rats in the present study. GK rats are non-obese models of type 2 diabetes established by selective inbreeding of Wistar rats based on impaired glucose tolerance. Though they start exhibiting only moderate hyperglycemia without changes in plasma insulin levels from 3 weeks postnatally, behavioral alterations in the open-field as well as significant impairments in memory retention compared with Wistar rats were observed at 10 weeks and were worsened at 20 weeks...
October 2016: International Journal of Developmental Neuroscience
Xiong Zhang, Bo Yu, Dan Yang, Zhengdong Qiao, Ting Cao, Peng Zhang
BACKGROUND: Roux-en-Y gastric bypass (RYGB) has shown positive outcomes in the remission of type 2 diabetes (T2D) and weight loss in obese patients by inhibiting food intake and nutrient absorption as well as inducing favorable hormonal changes. The purpose of the present study was to investigate whether gastric volume reduction is still required in addition to intestinal bypass for the purpose of T2D remission in nonobese patients. SETTING: University Medical Center...
April 20, 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
Inês Guerra Mollet, Helena Anna Malm, Anna Wendt, Marju Orho-Melander, Lena Eliasson
Altered microRNA profiles have been demonstrated in experimental models of type 2 diabetes, including in islets of the diabetic Goto-Kakizaki (GK) rat. Our bioinformatic analysis of conserved sequences in promoters of microRNAs, previously observed to be up-regulated in GK rat islets, revealed putative CGCG-core motifs on the promoter of the miR-212/miR-132 cluster, overexpression of which has been shown to increase insulin secretion. These motifs are possible targets of calmodulin binding transcription activators Camta1 and Camta2 that have been recognized as integrators of stress responses...
August 26, 2016: Journal of Biological Chemistry
Minako Karahashi, Yuko Hirata-Hanta, Kohei Kawabata, Daisuke Tsutsumi, Misaki Kametani, Nanako Takamatsu, Takeshi Sakamoto, Tohru Yamazaki, Satoshi Asano, Atsushi Mitsumoto, Yoichi Kawashima, Naomi Kudo
The Goto-Kakizaki (GK) rat is widely used as an animal model for spontaneous-onset type 2 diabetes without obesity; nevertheless, little information is available on the metabolism of fatty acids and triacylglycerols (TAG) in their livers. We investigated the mechanisms underlying the alterations in the metabolism of fatty acids and TAG in their livers, in comparison with Zucker (fa/fa) rats, which are obese and insulin resistant. Lipid profiles, the expression of genes for enzymes and proteins related to the metabolism of fatty acid and TAG, de novo synthesis of fatty acids and TAG in vivo, fatty acid synthase activity in vitro, fatty acid oxidation in liver slices, and very-low-density-lipoprotein (VLDL)-TAG secretion in vivo were estimated...
August 2016: Lipids
Trevor Hardigan, Abdul Yasir, Mohammed Abdelsaid, Maha Coucha, Sally El-Shaffey, Weiguo Li, Maribeth H Johnson, Adviye Ergul
The antihyperglycemic agent linagliptin, a dipeptidyl peptidase-4 (DPP-IV) inhibitor, has been shown to reduce inflammation and improve endothelial cell function. In this study, we hypothesized that DPP-IV inhibition with linagliptin would improve impaired cerebral perfusion in diabetic rats, as well as improve insulin-induced cerebrovascular relaxation and reverse pathological cerebrovascular remodeling. We further postulated that these changes would lead to a subsequent improvement of cognitive function. Male Type-2 diabetic and nondiabetic Goto-Kakizaki rats were treated with linagliptin for 4 wk, and blood glucose and DPP-IV plasma levels were assessed...
September 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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