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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
#1
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
#2
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
#3
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 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28843612/genomic-regulation-of-type-2-diabetes-endophenotypes-contribution-from-genetic-studies-in-the-goto-kakizaki-rat
#4
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/28821742/rock-1-mediates-diabetes-induced-retinal-pigment-epithelial-and-endothelial-cell-blebbing-contribution-to-diabetic-retinopathy
#5
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/28735866/microrna-193-5p-modulates-angiogenesis-through-igf2-in-type-2-diabetic-cardiomyopathy
#6
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...
July 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28689272/insulin-does-not-rescue-cortical-and-trabecular-bone-loss-in-type-2-diabetic-goto-kakizaki-rats
#7
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/28652790/sitagliptin-ameliorates-oxidative-stress-in-experimental-diabetic-nephropathy-by-diminishing-the-mir-200a-keap-1-nrf2-antioxidant-pathway
#8
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
#9
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/28637879/platelets-express-activated-p2y12-receptor-in-patients-with-diabetes-mellitus
#10
Liang Hu, Lin Chang, Yan Zhang, Lili Zhai, Shenghui Zhang, Zhiyong Qi, Hongmei Yan, Yan Yan, Xinping Luo, Si Zhang, Yiping Wang, Satya P Kunapuli, Hongying Ye, Zhongren Ding
BACKGROUND: Platelets from patients with diabetes mellitus are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes mellitus. However, the underlying mechanism of hyperactivated platelets is not completely understood. METHODS: We measured P2Y12 expression on platelets from patients with type 2 diabetes mellitus and on platelets from rats with diabetes mellitus...
August 29, 2017: Circulation
https://www.readbyqxmd.com/read/28633005/autophagy-impairment-mediated-by-s-nitrosation-of-atg4b-leads-to-neurotoxicity-in-response-to-hyperglycemia
#11
Yazi Li, Yuying Zhang, Lei Wang, Ping Wang, Yanhong Xue, Xiaopeng Li, Xinhua Qiao, Xu Zhang, Tao Xu, Guanghui Liu, Peng Li, Chang Chen
The majority of diabetic patients develop neuropathy and there is an increasing prevalence of neurodegeneration in the central nervous system (CNS). However, the mechanism behind this is poorly understood. Here we first observed that macroautophagy/autophagy was suppressed in the hippocampus of diabetic GK rats with hyperglycemia, whereas it was unchanged in ob/ob mice without hyperglycemia. Autophagy could be directly inhibited by high glucose in mouse primary hippocampal neurons. Moreover, autophagy was protective in high-glucose-induced neurotoxicity...
July 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28623340/adenovirus-mediated-suppression-of-hypothalamic-glucokinase-affects-feeding-behavior
#12
Romina María Uranga, Carola Millán, María José Barahona, Antonia Recabal, Magdiel Salgado, Fernando Martinez, Patricio Ordenes, Roberto Elizondo-Vega, Fernando Sepúlveda, Elena Uribe, María de Los Ángeles García-Robles
Glucokinase (GK), the hexokinase involved in glucosensing in pancreatic β-cells, is also expressed in arcuate nucleus (AN) neurons and hypothalamic tanycytes, the cells that surround the basal third ventricle (3V). Several lines of evidence suggest that tanycytes may be involved in the regulation of energy homeostasis. Tanycytes have extended cell processes that contact the feeding-regulating neurons in the AN, particularly, agouti-related protein (AgRP), neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) neurons...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607540/effects-of-high-fat-feeding-on-skeletal-muscle-gene-expression-in-diabetic-goto-kakizaki-rats
#13
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/28580522/antiangiogenic-effects-of-nerve-growth-factor-loop-4-monomeric-dipeptide-mimetic
#14
S A Kryzhanovskii, T A Antipova, I B Tsorin, E S Pekeldina, S V Nikolaev, A V Sorokina, I A Miroshkina, T A Gudasheva, S B Seredenin
The effects of GK-1, a monomeric dipeptide mimetic of nerve growth factor (NGF) loop 4, on angiogenesis were studied in vitro and in vivo. Experiments on human umbilical vein endothelial cells HUVEC showed that the test compound did not affect tubulogenesis (initial stage of angiogenesis) and prevented realization of the angiogenic effect of NGF and its dimeric dipeptide mimetic GK-2. Experiments on rat hind limb ischemia model demonstrated that GK-1 (1 mg/kg/day intraperitoneally over 14 days) significantly reduced the density of the capillary network in ischemic tissue and increased the number and area of Zenker necrosis in comparison with the control...
June 5, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28574832/impact-of-chronic-unpredicted-mild-stress-induced-depression-on-repaglinide-fate-via-glucocorticoid-signaling-pathway
#15
Hongyan Wei, Ting Zhou, Boyu Tan, Lei Zhang, Mingming Li, Zhijun Xiao, Feng Xu
Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats...
July 4, 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
#16
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
#17
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
https://www.readbyqxmd.com/read/28559245/temporal-transcriptomic-and-proteomic-landscapes-of-deteriorating-pancreatic-islets-in-type-2-diabetic-rats
#18
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. The process of deteriorating pancreatic islets, in which a complex network of molecular events is involved, is not yet fully characterized. We used RNA sequencing and tandem mass tag-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 data set outlines the dynamics of the 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, and the late stage (8-24 weeks) is characterized by inflammation amplification and compensation failure...
August 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
#19
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...
August 2017: Diabetologia
https://www.readbyqxmd.com/read/28541489/respiratory-effects-and-systemic-stress-response-following-acute-acrolein-inhalation-in-rats
#20
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 nonobese type II diabetic Wistar-derived model, were exposed by inhalation to 0, 2, or 4 ppm acrolein, 4 h/d for 1 or 2 days...
August 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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