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https://www.readbyqxmd.com/read/29325553/sitagliptin-improved-glucose-assimilation-in-detriment-of-fatty-acid-utilization-in-experimental-type-ii-diabetes-role-of-glp-1-isoforms-in-glut4-receptor-trafficking
#1
E Ramírez, B Picatoste, A González-Bris, M Oteo, F Cruz, A Caro-Vadillo, J Egido, J Tuñón, M A Morcillo, Ó Lorenzo
BACKGROUND: The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. METHODS: Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG)...
January 11, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29318456/voltage-dependence-of-the-ca2-transient-in-endocardial-and-epicardial-myocytes-from-the-left-ventricle-of-goto-kakizaki-type-2-diabetic-rats
#2
Lina Al Kury, Vadym Sydorenko, Manal M A Smail, Muhammad Anwar Qureshi, Anatoliy Shmygol, Murat Oz, Jaipaul Singh, Frank Christopher Howarth
Diabetes mellitus is a major global health disorder and, currently, over 450 million people have diabetes with 90% suffering from type 2 diabetes. Left untreated, diabetes may lead to cardiovascular diseases which are a leading cause of death in diabetic patients. Calcium is the trigger and regulator of cardiac muscle contraction and derangement in cellular Ca2+ homeostasis, which can result in heart failure and sudden cardiac death. It is of paramount importance to investigate the regional involvement of Ca2+ in diabetes-induced cardiomyopathy...
January 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29305881/liver-carbohydrates-metabolism-a-new-islet-neogenesis-associated-protein-peptide-ingap-pp-target
#3
Hernán Gonzalo Villagarcía, Carolina Lisi Román, María Cecilia Castro, Luisa Arbeláez González, María Teresa Ronco, Daniel Eleazar Francés, María Laura Massa, Bárbara Maiztegui, Luis Emilio Flores, Juan José Gagliardino, Flavio Francini
Islet-Neogenesis Associated Protein-Pentadecapeptide (INGAP-PP) increases β-cell mass and enhances glucose and amino acids-induced insulin secretion. Our aim was to demonstrate its effect on liver metabolism. For that purpose, adult male Wistar rats were injected twice-daily (10 days) with saline solution or INGAP-PP (250 μg). Thereafter, serum glucose, triglyceride and insulin levels were measured and homeostasis model assessment (HOMA-IR) and hepatic insulin sensitivity (HIS) were determined. Liver glucokinase and glucose-6-phosphatase (G-6-Pase) expression and activity, phosphoenolpyruvate carboxykinase (PEPCK) expression, phosphofructokinase-2 (PFK-2) protein content, P-Akt/Akt and glycogen synthase kinase-3β (P-GSK3/GSK3) protein ratios and glycogen deposit were also determined...
January 3, 2018: Peptides
https://www.readbyqxmd.com/read/29238302/sevoflurane-induces-exaggerated-and-persistent-cognitive-decline-in-a-type-ii-diabetic-rat-model-by-aggregating-hippocampal-inflammation
#4
Dongliang Li, Lingling Liu, Liang Li, Xingang Li, Bin Huang, Changqing Zhou, Zhaohang Zhang, Chunling Wang, Ping Dong, Xiyan Zhang, Bo Yang, Li Zhang
Recent studies show that a moderate duration of sevoflurane, one of the most commonly used volatile anesthetics in clinical practice, does not induce cognitive impairment in animals under physiological conditions. However, the influence of sevoflurane on cognitive function under diabetic conditions remains unclear. The aim of this study was to determine whether sevoflurane causes cognitive decline in a rat model of type 2 diabetes mellitus (DM) and if so, to explore a possible underlying mechanism. Diabetic Goto-Kakizaki (GK) rats and non-diabetic Wistar rats underwent 2...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29238211/interdependency-between-mechanical-parameters-and-afferent-nerve-discharge-in-remodeled-diabetic-goto-kakizaki-rat-intestine
#5
Jingbo Zhao, Jian Yang, Donghua Liao, Hans Gregersen
Background: Gastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system. Objective: We aimed to characterize the stimulus-response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/29220408/comparison-of-goto-kakizaki-rats-and-high-fat-diet-induced-obese-rats-are-they-reliable-models-to-study-type-2-diabetes-mellitus
#6
Wilson Mitsuo Tatagiba Kuwabara, Ana Carolina Panveloski-Costa, Caroline Naomi Fukusawa Yokota, Joice Naiara Bertaglia Pereira, Jorge Mancini Filho, Rosangela Pavan Torres, Sandro Massao Hirabara, Rui Curi, Tatiana Carolina Alba-Loureiro
Type 2 Diabetes mellitus (T2DM) is an evident growing disease that affects different cultures throughout the world. T2DM occurs under the influence of three main factors: the genetic background, environmental and behavioral components. Obesity is strongly associated to the development of T2DM in the occident, while in the orient most of the diabetic patients are considered lean. Genetics may be a key factor in the development of T2DM in societies where obesity is not a recurrent public health problem. Herein, two different models of rats were used to understand their differences and reliability as experimental models to study the pathophysiology of T2DM, in two different approaches: the genetic (GK rats) and the environmental (HFD-induced obese rats) influences...
2017: PloS One
https://www.readbyqxmd.com/read/29181667/comparison-of-the-pharmacological-effects-of-dimeric-dipeptide-nerve-growth-factor-mimetic-gk-2-and-mexidol-on-the-model-of-ischemic-stroke-in-rats
#7
P Yu Povarnina, A A Volkova, T A Gudasheva, S B Seredenin
We compared the effects of GK-2 (dimeric dipeptide mimetic of nerve growth factor) and Mexidol (standard preparation for the therapy of stroke) on rat model of transient occlusion of the middle cerebral artery. GK-2 and Mexidol were administered intraperitoneally in the most active doses (1 and 100 mg/kg, respectively) 6 h after surgery and then once a day for 6 days. The preparations reduced the volume of cerebral infarction (by 60 and 30%, respectively). At the same time, GK-2 had a pronounced and statistically more reliable effect in a dose that is lower by two orders of magnitude...
November 27, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29168078/the-effect-of-hypergastrinemia-following-sleeve-gastrectomy-and-pantoprazole-on-type-2-diabetes-mellitus-and-beta-cell-mass-in-goto-kakizaki-rats
#8
E Grong, C Nord, I B Arbo, M Eriksson, B E Kulseng, U Ahlgren, R Mårvik
PURPOSE: Metabolic surgery alters the secretion of gastrointestinal hormones that influence glycemic control. Elevated gastrin has been suggested to benefit patients with type 2 diabetes and has been reported following sleeve gastrectomy in rats. The present study compares the effect of hypergastrinemia following sleeve gastrectomy with proton-pump inhibitor therapy on glycemic control and beta-cell mass in lean, diabetic animals. METHODS: Thirty-three diabetic Goto-Kakizaki rats were randomized into pantoprazole + sham operation (GK-PPI), sleeve gastrectomy (GK-SG) and vehicle + sham operation (GK-V)...
November 22, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29167582/pyridoxine-dipharmacophore-derivatives-as-potent-glucokinase-activators-for-the-treatment-of-type-2-diabetes-mellitus
#9
Mikhail S Dzyurkevich, Denis A Babkov, Nikita V Shtyrlin, Olga Yu Mayka, Alfiya G Iksanova, Pavel M Vassiliev, Konstantin V Balakin, Alexander A Spasov, Vadim V Tarasov, George Barreto, Yurii G Shtyrlin, Gjumrakch Aliev
Glucokinase is one of the promising targets for glucose-lowering agents, and the development of GK activators are now considered as one of the most promising strategies for the treatment of type 2 diabetes mellitus. In this work, a series of novel symmetric molecular constructs, in which two pyridoxine moieties are connected via sulfur-containing linkers, have been synthesized and tested in vitro for glucokinase activation potential. The enzyme activation rates by two most active compounds at 100 μM (~150% and 130%) were comparable to that of the reference agent PF-04937319 (~154%)...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142323/nkx6-1-decline-accompanies-mitochondrial-dna-reduction-but-subtle-nucleoid-size-decrease-in-pancreatic-islet-%C3%AE-cells-of-diabetic-goto-kakizaki-rats
#10
Tomáš Špaček, Vojtěch Pavluch, Lukáš Alán, Nikola Capková, Hana Engstová, Andrea Dlasková, Zuzana Berková, František Saudek, Petr Ježek
Hypertrophic pancreatic islets (PI) of Goto Kakizaki (GK) diabetic rats contain a lower number of β-cells vs. non-diabetic Wistar rat PI. Remaining β-cells contain reduced mitochondrial (mt) DNA per nucleus (copy number), probably due to declining mtDNA replication machinery, decreased mt biogenesis or enhanced mitophagy. We confirmed mtDNA copy number decrease down to <30% in PI of one-year-old GK rats. Studying relations to mt nucleoids sizes, we employed 3D superresolution fluorescent photoactivable localization microscopy (FPALM) with lentivirally transduced Eos conjugate of mt single-stranded-DNA-binding protein (mtSSB) or transcription factor TFAM; or by 3D immunocytochemistry...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137481/effects-of-pioglitazone-on-ventricular-myocyte-shortening-and-ca-2-transport-in-the-goto-kakizaki-type-2-diabetic-rat
#11
K A Salem, V Sydorenko, M Qureshi, M Oz, F C Howarth
Pioglitazone (PIO) is a thiazolidindione antidiabetic agent which improves insulin sensitivity and reduces blood glucose in experimental animals and treated patients. At the cellular level the actions of PIO in diabetic heart are poorly understood. A previous study has demonstrated shortened action potential duration and inhibition of a variety of transmembrane currents including L-type Ca(2+) current in normal canine ventricular myocytes. The effects of PIO on shortening and calcium transport in ventricular myocytes from the Goto-Kakizaki (GK) type 2 diabetic rat have been investigated...
November 10, 2017: Physiological Research
https://www.readbyqxmd.com/read/29122960/mir-335-overexpression-impairs-insulin-secretion-through-defective-priming-of-insulin-vesicles
#12
Vishal A Salunkhe, Jones K Ofori, Nikhil R Gandasi, Sofia A Salö, Sofia Hansson, Markus E Andersson, Anna Wendt, Sebastian Barg, Jonathan L S Esguerra, Lena Eliasson
MicroRNAs contribute to the maintenance of optimal cellular functions by fine-tuning protein expression levels. In the pancreatic β-cells, imbalances in the exocytotic machinery components lead to impaired insulin secretion and type 2 diabetes (T2D). We hypothesize that dysregulated miRNA expression exacerbates β-cell dysfunction, and have earlier shown that islets from the diabetic GK-rat model have increased expression of miRNAs, including miR-335-5p (miR-335). Here, we aim to determine the specific role of miR-335 during development of T2D, and the influence of this miRNA on glucose-stimulated insulin secretion and Ca(2+)-dependent exocytosis...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29053717/gpr40-partial-agonists-and-agopams-differentiating-effects-on-glucose-and-hormonal-secretions-in-the-rodent
#13
Michele J Pachanski, Melissa E Kirkland, Daniel T Kosinski, Joel Mane, Boonlert Cheewatrakoolpong, Jiyan Xue, Daphne Szeto, Gail Forrest, Corin Miller, Michelle Bunzel, Christopher W Plummer, Harry R Chobanian, Michael W Miller, Sarah Souza, Brande S Thomas-Fowlkes, Aimie M Ogawa, Adam B Weinglass, Jerry Di Salvo, Xiaoyan Li, Yue Feng, Daniel A Tatosian, Andrew D Howard, Steven L Colletti, Maria E Trujillo
GPR40 agonists are effective antidiabetic agents believed to lower glucose through direct effects on the beta cell to increase glucose stimulated insulin secretion. However, not all GPR40 agonists are the same. Partial agonists lower glucose through direct effects on the pancreas, whereas GPR40 AgoPAMs may incorporate additional therapeutic effects through increases in insulinotrophic incretins secreted by the gut. Here we describe how GPR40 AgoPAMs stimulate both insulin and incretin secretion in vivo over time in diabetic GK rats...
2017: PloS One
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
#14
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
#15
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-nonobese-type-2-diabetic-goto-kakizaki-gk-rats
#16
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 nonobese 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 two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) (n = 6/subgroup)...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28917976/low-molecular-weight-fucoidan-ameliorates-hindlimb-ischemic-injury-in-type-2-diabetic-rats
#17
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/28843612/genomic-regulation-of-type-2-diabetes-endophenotypes-contribution-from-genetic-studies-in-the-goto-kakizaki-rat
#18
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
#19
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
#20
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
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