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https://www.readbyqxmd.com/read/28971314/alterations-of-brain-energy-metabolism-in-type-2-diabetic-goto-kakizaki-rats-measured-in-vivo-by-13-c-magnetic-resonance-spectroscopy
#1
Freya-Merret Girault, Sarah Sonnay, Rolf Gruetter, João M N Duarte
Type 2 diabetes (T2D) is associated with deterioration of brain structure and function. Here, we tested the hypothesis that T2D induces a reorganization of the brain metabolic networks that support brain function. For that, alterations of neuronal and glial energy metabolism were investigated in a T2D model, the Goto-Kakizaki (GK) rat. (13)C magnetic resonance spectroscopy in vivo at 14.1 T was used to detect (13)C labeling incorporation into carbons of glutamate, glutamine, and aspartate in the brain of GK (n = 7) and Wistar (n = 13) rats during intravenous [1,6-(13)C]glucose administration...
October 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28928461/time-dependent-effects-of-ipragliflozin-on-behaviour-and-energy-homeostasis-in-normal-and-type-2-diabetic-rats-continuous-glucose-telemetry-analysis
#2
Hiroyuki Iuchi, Masaya Sakamoto, Daisuke Matsutani, Hirofumi Suzuki, Yosuke Kayama, Norihiko Takeda, Susumu Minamisawa, Kazunori Utsunomiya
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote urinary glucose excretion. Conversely, they cause behavioural changes, such as hyperphagia, that result in a positive energy balance. The relationship between energy homeostasis and SGLT2 inhibitors-induced behavioural changes remains unclear. Here we show that ipragliflozin, a SGLT2 inhibitor, time-dependently affects behaviour and enhances energy expenditure in normal and type 2 diabetic Goto-Kakizaki (GK) rats, using continuous glucose telemetry...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923829/estrogen-deprivation-aggravates-cardiac-hypertrophy-in-non-obese-type-2-diabetic-goto-kakizaki-gk-rats
#3
Nattayaporn Apaijai, Narattaphol Charoenphandhu, Jitjiroj Ittichaichareon, Panan Suntornsaratoon, Nateetip Krishnamra, Ratchaneevan Aeimlapa, Siriporn C Chattipakorn, Nipon Chattipakorn
Both type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling.  However, the role of estrogen deprivation on adverse cardiac remodeling in non-obese T2DM rats has not been clearly elucidated.  We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto-Kakizaki (GK) rats.  Wild-type (WT) and GK rats at the age of 9 months old were divided into 2 subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) (n=6/subgroup)...
September 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28917976/low-molecular-weight-fucoidan-ameliorates-hindlimb-ischemic-injury-in-type-2-diabetic-rats
#4
Zhiqiang Wang, Tiantian Liu, Xiaoping Chen, Hongjie You, Quanbin Zhang, Jingyi Xue, Yuanyuan Zheng, Dali Luo
ETHNOPHARMACOLOGICAL RELEVANCE: Low molecular weight fucoidan (LMWF), extracted from Laminaria japonica Areschoug, is a traditional Chinese medicine, commonly used to alleviate edema, particularly for feet with numbness and pain. AIM OF THE STUDY: Diabetic mellitus (DM) patients are at high risk of developing peripheral arterial disease (PAD). Individuals with DM and PAD co-morbidity have a much higher risk of critical limb ischemia. LMWF showed several beneficial effects, such as anti-inflammation, anti-thrombosis, and enhancing revascularization...
September 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28911974/molecular-genetics-of-the-transcription-factor-glis3-identifies-its-dual-function-in-beta-cells-and-neurons
#5
Sophie Calderari, Massimiliano Ria, Christelle Gérard, Tatiane C Nogueira, Olatz Villate, Stephan C Collins, Helen Neil, Nicolas Gervasi, Christophe Hue, Nicolas Suarez-Zamorano, Cécilia Prado, Miriam Cnop, Marie-Thérèse Bihoreau, Pamela J Kaisaki, Jean-Baptiste Cazier, Cécile Julier, Mark Lathrop, Michel Werner, Decio L Eizirik, Dominique Gauguier
The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q<0.05; enrichment range 1.40-9.11 fold) sharing the motif wrGTTCCCArTAGs, which were enriched in genes involved in neuronal function and autophagy and in risk genes for metabolic and neuro-behavioural diseases. We confirmed experimentally Glis3-mediated regulation of the expression of genes involved in autophagy and neuron function in INS1 and neuronal PC12 cells...
September 11, 2017: Genomics
https://www.readbyqxmd.com/read/28843612/genomic-regulation-of-type-2-diabetes-endophenotypes-contribution-from-genetic-studies-in-the-goto-kakizaki-rat
#6
REVIEW
Marie-Thérèse Bihoreau, Marc-Emmanuel Dumas, Mark Lathrop, Dominique Gauguier
The inbred Goto-Kakizaki (GK) rat strain is a unique model of spontaneous type 2 diabetes mellitus caused by naturally occurring genetic variants that have been selectively isolated from an outbred colony of Wistar rats. Genetic and genomic studies that we designed with Alain Ktorza in experimental crosses and congenic strains of the GK have shed light on the complex etiopathogenesis of diabetes phenotypes in this model. Diabetes-related phenotypes in the GK are under polygenic control and distinct genetic loci regulate glucose tolerance, insulin secretion, β-cell mass and plasma lipids...
August 23, 2017: Biochimie
https://www.readbyqxmd.com/read/28840975/cardioprotection-mediated-by-exosomes-is-impaired-in-the-setting-of-type-ii-diabetes-but-can-be-rescued-by-the-use-of-non-diabetic-exosomes-in-vitro
#7
Sean M Davidson, Jaime A Riquelme, Kaloyan Takov, Jose M Vicencio, Claire Boi-Doku, Vanessa Khoo, Christian Doreth, Dina Radenkovic, Sergio Lavandero, Derek M Yellon
Many patients with ischaemic heart disease also have diabetes. As myocardial infarction is a major cause of mortality and morbidity in these patients, treatments that increase cell survival in response to ischaemia and reperfusion are needed. Exosomes-nano-sized, lipid vesicles released from cells-can protect the hearts of non-diabetic rats. We previously showed that exosomal HSP70 activates a cardioprotective signalling pathway in cardiomyocytes culminating in ERK1/2 and HSP27 phosphorylation. Here, we investigated whether the exosomal cardioprotective pathway remains intact in the setting of type II diabetes...
August 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28821742/rock-1-mediates-diabetes-induced-retinal-pigment-epithelial-and-endothelial-cell-blebbing-contribution-to-diabetic-retinopathy
#8
Pierre-Raphaël Rothschild, Sawsen Salah, Marianne Berdugo, Emmanuelle Gélizé, Kimberley Delaunay, Marie-Christine Naud, Christophe Klein, Alexandre Moulin, Michèle Savoldelli, Ciara Bergin, Jean-Claude Jeanny, Laurent Jonet, Yvan Arsenijevic, Francine Behar-Cohen, Patricia Crisanti
In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28805970/a-novel-free-fatty-acid-receptor-1-gpr40-ffar1-agonist-mr1704-enhances-glucose-dependent-insulin-secretion-and-improves-glucose-homeostasis-in-rats
#9
Naoto Tsuda, Atsuko Kawaji, Toshihiro Sato, Mitsuhiro Takagi, Chika Higashi, Yutaka Kato, Kumiko Ogawa, Hiroyasu Naba, Munetaka Ohkouchi, Masaki Nakamura, Yoshitaka Hosaka, Junichi Sakaki
Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats. Treatment of rat islets with MR1704 increased glucose-dependent insulin secretion...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28735866/microrna-193-5p-modulates-angiogenesis-through-igf2-in-type-2-diabetic-cardiomyopathy
#10
Fan Yi, Yuqiang Shang, Bing Li, Shilin Dai, Wei Wu, Long Cheng, Xiancan Wang
BACKGROUND: Patients with diabetic cardiomyopathy are often associated with increasing risk of heart failure. In this work, we used animal model to characterize the angiogenic effect of microRNA-193-5p, miR-193-5p in type 2 diabetic Goto-Kakizaki (GK) rats' myocardial microvascular endothelial cells, MMEC(GK). METHODS: MiR-193-5p in MMEC(GK) was compared to its expression in Wistar rat MMEC. In MMEC(GK), miR-193-5p was downregulated through viral infection. Its angiogenic effects on MMEC(GK) migration and proliferation were assessed by transwell and MTT assays, respectively...
September 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28720074/regeneration-of-long-distance-peripheral-nerve-defects-after-delayed-reconstruction-in-healthy-and-diabetic-rats-is-supported-by-immunomodulatory-chitosan-nerve-guides
#11
Lena Stenberg, Maria Stößel, Giulia Ronchi, Stefano Geuna, Yaobin Yin, Susanne Mommert, Lisa Mårtensson, Jennifer Metzen, Claudia Grothe, Lars B Dahlin, Kirsten Haastert-Talini
BACKGROUND: Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve guides (CNGs) have recently been introduced as a new generation of medical devices for immediate peripheral nerve reconstruction. Here, CNGs were used for 45 days delayed reconstruction of critical length 15 mm rat sciatic nerve defects in either healthy Wistar rats or diabetic Goto-Kakizaki rats; the latter resembling type 2 diabetes...
July 18, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28711973/piwi-interacting-rnas-as-novel-regulators-of-pancreatic-beta-cell-function
#12
Imène Sarah Henaoui, Cécile Jacovetti, Inês Guerra Mollet, Claudiane Guay, Jonathan Sobel, Lena Eliasson, Romano Regazzi
AIMS/HYPOTHESIS: P-element induced Wimpy testis (PIWI)-interacting RNAs (piRNAs) are small non-coding RNAs that interact with PIWI proteins and guide them to silence transposable elements. They are abundantly expressed in germline cells and play key roles in spermatogenesis. There is mounting evidence that piRNAs are also present in somatic cells, where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta cell activities...
July 16, 2017: Diabetologia
https://www.readbyqxmd.com/read/28689272/insulin-does-not-rescue-cortical-and-trabecular-bone-loss-in-type-2-diabetic-goto-kakizaki-rats
#13
Ratchaneevan Aeimlapa, Narattaphol Charoenphandhu, Panan Suntornsaratoon, Kannikar Wongdee, Wacharaporn Tiyasatkulkovit, Kanchana Kengkoom, Nateetip Krishnamra
In type 2 diabetes mellitus (T2DM), the decreased bone strength is often associated with hyperglycemia and bone cell insulin resistance. Since T2DM is increasingly reported in young adults, it is not known whether the effect of T2DM on bone would be different in young adolescents and aging adults. Here, we found shorter femoral and tibial lengths in 7-month, but not 13-month, Goto-Kakizaki (GK) T2DM rats as compared to wild-type rats. Bone µCT analysis showed long-lasting impairment of both cortical and trabecular bones in GK rats...
July 8, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28658037/investigation-of-the-effect-of-diabetes-on-radiculopathy-induced-by-nucleus-pulposus-application-to-the-drg-in-a-spontaneously-diabetic-rat-model
#14
Takuya Kameda, Miho Sekiguchi, Yoichi Kaneuchi, Shin-Ichi Konno
STUDY DESIGN: Controlled, interventional animal study. OBJECTIVE: To evaluate the effect of diabetes mellitus (DM) on radiculopathy due to lumbar disc herniation (LDH), by investigating pain-related behavior and the expression of tumor necrosis factor-alpha (TNF-α) and growth-associated protein 43 (GAP43) in type 2 diabetic rats following application of nucleus pulposus (NP) to the dorsal root ganglion (DRG). SUMMARY OF BACKGROUND DATA: Previous clinical studies suggested negative effects of DM on radiculopathy due to LDH, and that inflammation and nerve regeneration could interact with DM and radiculopathy...
June 27, 2017: Spine
https://www.readbyqxmd.com/read/28652790/sitagliptin-ameliorates-oxidative-stress-in-experimental-diabetic-nephropathy-by-diminishing-the-mir-200a-keap-1-nrf2-antioxidant-pathway
#15
Esther Civantos, Enrique Bosch, Elisa Ramirez, Olha Zhenyukh, Jesús Egido, Oscar Lorenzo, Sebastián Mas
BACKGROUND: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor used in type 2 diabetes therapy, has demonstrated protective effects in diabetic chronic kidney disease, in part due to its pleiotropic actions. However, its potential direct effects on the kidney are still not completely defined. Here, by means of proteomics and miRNA profiling, we have further unveiled the role of sitagliptin in oxidative stress, as well as the underlying mechanisms. METHODS: Renal cortex samples from 9-month-old wild-type (Wistar), type II diabetic Goto-Kakizaki (GK) and sitagliptin-treated GK rats (GK+Sita) (10 mg kg(-1) per day) were subjected to quantitative miRNA transcriptomic array, immunohistochemistry and Western blot studies...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28652187/hyperglycemia-induced-the-alzheimer-s-proteins-and-promoted-loss-of-synaptic-proteins-in-advanced-age-female-goto-kakizaki-gk-rats
#16
Hiranya Pintana, Nattayaporn Apaijai, Sasiwan Kerdphoo, Wasana Pratchayasakul, Jirapas Sripetchwandee, Panan Suntornsaratoon, Narattaphol Charoenphandhu, Nipon Chattipakorn, Siriporn C Chattipakorn
Although both type 2 diabetes mellitus (T2DM) and aging are related with Alzheimer's disease (AD), the effects of aging on the Alzheimer's proteins and the synaptic markers in T2DM have not been investigated. This study, we hypothesized that T2DM rats with advanced-age, aggravates the reduction of synaptic proteins and an increase in the Alzheimer's protein markers. Goto-Kakizaki rats (GK) were used as a T2DM group and wild-type rats (WT) were used as a control group. Rats in each group were categorized by age into young-adult (7 months) and advanced-age rats (12...
August 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28607540/effects-of-high-fat-feeding-on-skeletal-muscle-gene-expression-in-diabetic-goto-kakizaki-rats
#17
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
#18
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
#19
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
#20
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...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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