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GK rat

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
Nils Rademacher, Bettina Schmerl, Jennifer A Lardong, Markus C Wahl, Sarah A Shoichet
At neuronal synapses, multiprotein complexes of trans-synaptic adhesion molecules, scaffold proteins and neurotransmitter receptors assemble to essential building blocks required for synapse formation and maintenance. Here we describe a novel role for the membrane-associated guanylate kinase (MAGUK) protein MPP2 (MAGUK p55 subfamily member 2) at synapses of rat central neurons. Through interactions mediated by its C-terminal SH3-GK domain module, MPP2 binds to the abundant postsynaptic scaffold proteins PSD-95 and GKAP and localises to postsynaptic sites in hippocampal neurons...
October 19, 2016: Scientific Reports
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
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
S A Kryzhanovskii, T A Antipova, I B Tsorin, E S Pekeldina, V N Stolyaruk, S V Nikolaev, A V Sorokina, T A Gudasheva, S B Seredenin
Angiogenic action of compound GK-2, a dimeric dipeptide mimetic of loop 4 of nerve growth factor (NGF), was studied in in vitro and in vivo experiments. Experiments on human endothelial cell culture HUVEC showed that compound GK-2 significantly (p<0.05) stimulated the initial stage of angiogenesis, and its angiogenic activity was not inferior to the reference neurotrophin NGF. In experiments with hindlimb ischemia modeled in rats, GK-2 (1 mg/kg intraperitoneally for 14 days) significantly increased the total length of capillary vessels (p<0...
August 2016: Bulletin of Experimental Biology and Medicine
Wenhui Liu, Wenbin Zhao, Jun Lai, Qi Shen, Yingchun Xu, Liqiang Pan, Shuqing Chen
Human serum albumin (HSA) and Interleukin-1 receptor antagonist (IL1Ra) fusion protein is a potential long-acting drug in the treatment of type 2 diabetes. Previously, the expression level of HSA/IL1Ra in Pichia pastoris was successfully improved by increasing the gene copy number and co-expression with chaperone (Protein disulfide isomerase, PDI) in our lab. However, the overexpression strain (OE-Strain) resulted in low production in high-cell-density fermentation. In this study, the culture medium had been optimized in both flask and fermenter, and the optimum culture medium notably increased the productivity and stability of HSA/IL1Ra...
August 30, 2016: Biotechnology and Applied Biochemistry
Vini Nagaraj, Abdulla S Kazim, Johan Helgeson, Clemens Lewold, Satadal Barik, Pawel Buda, Thomas M Reinbothe, Stefan Wennmalm, Enming Zhang, Erik Renström
Elevated basal insulin secretion under fasting conditions together with insufficient stimulated insulin release is an important hallmark of type 2 diabetes, but the mechanisms controlling basal insulin secretion remain unclear. Membrane rafts exist in pancreatic islet cells and spatially organize membrane ion channels and proteins controlling exocytosis, which may contribute to the regulation of insulin secretion. Membrane rafts (cholesterol and sphingolipid containing microdomains) were dramatically reduced in human type 2 diabetic and diabetic Goto-Kakizaki (GK) rat islets when compared with healthy islets...
October 2016: Molecular Endocrinology
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
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
Mamoru Uemura, Isumi Toda, Wataru Kawashima, Gaku Yoshimoto, Yi-Ru Fang, Yuan Jin Xu, Yuan Liu, Lei Zhang, Akimichi Takemura
The objective of this study was to evaluate morphological changes at the articular disc of the temporomandibular joint and capillary of the retrodiscal tissue in a rat model for type 2 spontaneous diabetes mellitus (DM) (i.e., Goto-Kakizaki [GK] rats) compared to normal Wistar rats. A total of 20 experimental rats were used in this study; the rats were categorized into the normal (n = 10 male 8-week-old Wistar rats) and DM (n = 10 male 8-week-old GK rats) groups. Hematoxylin-eosin stained specimens were obtained from 5 rats from each group...
2016: Okajimas Folia Anatomica Japonica
Masaya Hosokawa, Michiko Katsukawa, Hiroshi Tanaka, Hitomi Fukuda, Sonomi Okuno, Kinsuke Tsuda, Nobuko Iritani
Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed...
May 2016: Journal of Clinical Biochemistry and Nutrition
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