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https://www.readbyqxmd.com/read/28689272/insulin-does-not-rescue-cortical-and-trabecular-bone-loss-in-type-2-diabetic-goto-kakizaki-rats
#1
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
#2
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
#3
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...
June 24, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28637879/platelets-express-activated-p2y12-receptor-in-patients-with-diabetes
#4
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 are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes. 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 (T2DM) and on platelets from rats with diabetes. We also assayed platelet P2Y12 activation by measuring cAMP and VASP phosphorylation...
June 21, 2017: Circulation
https://www.readbyqxmd.com/read/28633005/autophagy-impairment-mediated-by-s-nitrosation-of-atg4b-leads-to-neurotoxicity-in-response-to-hyperglycemia
#5
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 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...
June 20, 2017: Autophagy
https://www.readbyqxmd.com/read/28623340/adenovirus-mediated-suppression-of-hypothalamic-glucokinase-affects-feeding-behavior
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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/28541489/respiratory-effects-and-systemic-stress-response-following-acute-acrolein-inhalation-in-rats
#14
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
#15
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
#16
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/28428961/glucose-insulin-potassium-alleviates-intestinal-mucosal-barrier-injuries-involving-decreased-expression-of-uncoupling-protein-2-and-nlr-family-pyrin-domain-containing-3-inflammasome-in-polymicrobial-sepsis
#17
Jun-Liang Zhang, Yi-Ting Chen, Guang-Dao Chen, Tao Wang, Ju-Xin Zhang, Qi-Yi Zeng
Uncoupling protein 2 (UCP2) may be critical for intestinal barrier function which may play a key role in the development of sepsis, and insulin has been reported to have anti-inflammatory effects. Male Sprague-Dawley rats were randomly allocated into five groups: control group, cecal ligation and puncture (CLP) group, sham surgery group, CLP plus glucose-insulin-potassium (GIK) group, and CLP plus glucose and potassium (GK) group. Ileum tissues were collected at 24 h after surgery. Histological and cytokine analyses, intestinal permeability tests, and western blots of intestinal epithelial tight junction component proteins and UCP2 were performed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28392387/functionally-modified-polyacrylamide-graft-gum-karaya-ph-sensitive-spray-dried-microspheres-for-colon-targeting-of-an-anti-cancer-drug
#18
Vijaykumar V Alange, Ravindra P Birajdar, Raghavendra V Kulkarni
An effort was made to formulate and evaluate pH-sensitive spray dried microspheres using hydrolyzed polyacrylamide-graft-gum karaya (PAAm-g-GK) for colon specific delivery of an anti-cancer agent, capecitabine. The synthesis of pH-sensitive PAAm-g-GK copolymer was done by free radical polymerization followed by alkaline hydrolysis and characterized satisfactorily. The microspheres were spherical in shape; drug entrapment efficiency was found to be in the range of 77.30% to 88.74%. Pulsatile swelling study indicates that the PAAm-g-GK consists of considerable pH-sensitivity...
September 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28348018/synergistic-interaction-of-hypertension-and-diabetes-in-promoting-kidney-injury-and-the-role-of-endoplasmic-reticulum-stress
#19
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/28315330/microrna-29-regulates-myocardial-microvascular-endothelial-cells-proliferation-and-migration-in-association-with-igf1-in-type-2-diabetes
#20
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
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