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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
#1
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
#2
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/28360538/antidiabetic-and-gastric-emptying-inhibitory-effect-of-herbal-melia-azedarach-leaf-extract-in-rodent-models-of-diabetes-type-2-mellitus
#3
Daniel Seifu, Lars E Gustafsson, Rajinder Chawla, Solomon Genet, Asfaw Debella, Mikael Holst, Per M Hellström
Diabetes type 2 is associated with impaired insulin production and increased insulin resistance. Treatment with antidiabetic drugs and insulin strives for normalizing glucose homeostasis. In Ethiopian traditional medicine, plant extracts of Melia azedarach are used to control diabetes mellitus and various gastrointestinal disorders. The objective of this study was to clarify the antidiabetic effects of M. azedarach leaf extracts in diabetic type 2 experimental animals. In this study, mice were injected with Melia extract intraperitoneally...
2017: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/28348018/synergistic-interaction-of-hypertension-and-diabetes-in-promoting-kidney-injury-and-the-role-of-endoplasmic-reticulum-stress
#4
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/28332581/elevated-mir-130a-mir130b-mir-152-expression-reduces-intracellular-atp-levels-in-the-pancreatic-beta-cell
#5
Jones K Ofori, Vishal A Salunkhe, Annika Bagge, Neelanjan Vishnu, Mototsugu Nagao, Hindrik Mulder, Claes B Wollheim, Lena Eliasson, Jonathan L S Esguerra
MicroRNAs have emerged as important players of gene regulation with significant impact in diverse disease processes. In type-2 diabetes, in which impaired insulin secretion is a major factor in disease progression, dysregulated microRNA expression in the insulin-secreting pancreatic beta cell has been widely-implicated. Here, we show that miR-130a-3p, miR-130b-3p, and miR-152-3p levels are elevated in the pancreatic islets of hyperglycaemic donors, corroborating previous findings about their upregulation in the islets of type-2 diabetes model Goto-Kakizaki rats...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315330/microrna-29-regulates-myocardial-microvascular-endothelial-cells-proliferation-and-migration-in-association-with-igf1-in-type-2-diabetes
#6
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
https://www.readbyqxmd.com/read/28299342/relationship-between-immunological-abnormalities-in-rat-models-of-diabetes-mellitus-and-the-amplification-circuits-for-diabetes
#7
REVIEW
Yuji Takeda, Tomoko Shimomura, Hironobu Asao, Ichiro Wakabayashi
A better understanding of pathogenic mechanisms is required in order to treat diseases. However, the mechanisms of diabetes mellitus and diabetic complications are extremely complex. Immune reactions are involved in the pathogenesis of diabetes and its complications, while diabetes influences immune reactions. Furthermore, both diabetes and immune reactions are influenced by genetic and environmental factors. To address these issues, animal models are useful tools. So far, various animal models of diabetes have been developed in rats, which have advantages over mice models in terms of the larger volume of tissue samples and the variety of type 2 diabetes models...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28275538/analysis-of-significantly-mutated-genes-as-a-clinical-tool-for-the-diagnosis-in-a-case-of-lung-cancer
#8
Yoshihiro Miyashita, Yosuke Hirotsu, Toshiharu Tsutsui, Seishi Higashi, Yusuke Sogami, Yumiko Kakizaki, Taichiro Goto, Kenji Amemiya, Toshio Oyama, Masao Omata
Bronchoendoscopic examination is not necessarily comfortable procedure and limited by its sensitivity, depending on the location and size of the tumor lesion. Patients with a non-diagnostic bronchoendoscopic examination often undergo further invasive examinations. Non-invasive diagnostic tool of lung cancer is desired. A 72-year-old man had a 3.0 cm × 2.5 cm mass lesion in the segment B1 of right lung. Cytological examination of sputum, bronchial washing and curetted samples were all "negative". We could confirm a diagnosis of lung cancer after right upper lung lobe resection pathologically, and also obtained concordant results by genomic analysis using cytological negative samples from airways collected before operation...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28214972/avocado-oil-induces-long-term-alleviation-of-oxidative-damage-in-kidney-mitochondria-from-type-2-diabetic-rats-by-improving-glutathione-status
#9
Omar Ortiz-Avila, María Del Consuelo Figueroa-García, Claudia Isabel García-Berumen, Elizabeth Calderón-Cortés, Jorge A Mejía-Barajas, Alain R Rodriguez-Orozco, Ricardo Mejía-Zepeda, Alfredo Saavedra-Molina, Christian Cortés-Rojo
Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion...
February 18, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28207836/tmg-123-a-novel-glucokinase-activator-exerts-durable-effects-on-hyperglycemia-without-increasing-triglyceride-in-diabetic-animal-models
#10
Yoshinori Tsumura, Yu Tsushima, Azusa Tamura, Makiko Hasebe, Masanobu Kanou, Hirotsugu Kato, Tsunefumi Kobayashi
Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues...
2017: PloS One
https://www.readbyqxmd.com/read/28197316/design-and-synthesis-of-novel-selective-gpr40-agopams
#11
Christopher W Plummer, Matthew J Clements, Helen Chen, Murali Rajagopalan, Hubert Josien, William K Hagmann, Michael Miller, Maria E Trujillo, Melissa Kirkland, Daniel Kosinski, Joel Mane, Michele Pachanski, Boonlert Cheewatrakoolpong, Andrew F Nolting, Robert Orr, Melodie Christensen, Louis-Charles Campeau, Michael J Wright, Randal Bugianesi, Sarah Souza, Xiaoping Zhang, Jerry Di Salvo, Adam B Weinglass, Richard Tschirret-Guth, Ravi Nargund, Andrew D Howard, Steven L Colletti
GPR40 is a G-protein-coupled receptor expressed primarily in pancreatic islets and intestinal L-cells that has been a target of significant recent therapeutic interest for type II diabetes. Activation of GPR40 by partial agonists elicits insulin secretion only in the presence of elevated blood glucose levels, minimizing the risk of hypoglycemia. GPR40 agoPAMs have shown superior efficacy to partial agonists as assessed in a glucose tolerability test (GTT). Herein, we report the discovery and optimization of a series of potent, selective GPR40 agoPAMs...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28163042/munc18b-increases-insulin-granule-fusion-restoring-deficient-insulin-secretion-in-type-2-diabetes-human-and-goto-kakizaki-rat-islets-with-improvement-in-glucose-homeostasis
#12
Tairan Qin, Tao Liang, Dan Zhu, Youhou Kang, Li Xie, Subhankar Dolai, Shuzo Sugita, Noriko Takahashi, Claes-Goran Ostenson, Kate Banks, Herbert Y Gaisano
Reduced pancreatic islet levels of Munc18a/SNARE complex proteins have been postulated to contribute to the deficient glucose-stimulated insulin secretion (GSIS) in type-2 diabetes (T2D). Whereas much previous work has purported Munc18a/SNARE complex (Syntaxin-1A/VAMP-2/SNAP25) to be primarily involved in predocked secretory granule (SG) fusion, less is known about newcomer SGs that undergo minimal docking time at the plasma membrane before fusion. Newcomer SG fusion has been postulated to involve a distinct SM/SNARE complex (Munc18b/Syntaxin-3/VAMP8/SNAP25), whose levels we find also reduced in islets of T2D humans and T2D Goto-Kakizaki (GK) rats...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28122008/compromised-neurotrophic-and-angiogenic-regenerative-capability-during-tendon-healing-in-a-rat-model-of-type-ii-diabetes
#13
Aisha S Ahmed, Jian Li, Alim M D Abdul, Mahmood Ahmed, Claes-Göran Östenson, Paul T Salo, Carolyn Hewitt, David A Hart, Paul W Ackermann
Metabolic diseases such as diabetes mellitus type-II (DM-II) may increase the risk of suffering painful connective tissue disorders and tendon ruptures. The pathomechanisms, however, by which diabetes adversely affects connective tissue matrix metabolism and regeneration, still need better definition. Our aim was to study the effect of DM-II on expressional changes of neuro- and angiotrophic mediators and receptors in intact and healing Achilles tendon. The right Achilles tendon was transected in 5 male DM-II Goto-Kakizaki (GK) and 4 age-matched Wistar control rats...
2017: PloS One
https://www.readbyqxmd.com/read/28118732/relationship-between-pdk1-and-contraction-in-carotid-arteries-in-goto-kakizaki-rat-a-spontaneous-type-2-diabetic-animal-model
#14
Shun Watanabe, Takayuki Matsumoto, Kumiko Taguchi, Tsuneo Kobayashi
We studied the relationship between 3-phosphoinositide-dependent protein kinase 1 (PDK1) and contractions induced by serotonin, phenylephrine, and thromboxane A2 mimetic (U46619) in the presence of nitric oxide synthase inhibitor in the carotid arteries of Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic model, in the chronic stage of disease. Serotonin-induced contraction was greater in the GK rats than in the control Wistar rats. A specific PDK1 inhibitor (GSK2334470) decreased the serotonin-induced contraction in the GK rats but not in the Wistar rats, and the difference in such contraction was abolished with this treatment...
January 24, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28116460/enhanced-vegf-signalling-mediates-cerebral-neovascularisation-via-downregulation-of-guidance-protein-robo4-in-a-rat-model-of-diabetes
#15
Mohammed Abdelsaid, Maha Coucha, Sherif Hafez, Abdul Yasir, Maribeth H Johnson, Adviye Ergul
AIMS/HYPOTHESIS: Diabetes promotes cerebral neovascularisation via increased vascular endothelial growth factor (VEGF) angiogenic signalling. Roundabout-4 (ROBO4) protein is an endogenous inhibitor of VEGF signalling that stabilises the vasculature. Yet, how diabetes affects ROBO4 function remains unknown. We hypothesised that increased VEGF signalling in diabetes decreases ROBO4 expression and function via binding of ROBO4 with VEGF-activated β3 integrin and that restoration of ROBO4 expression prevents/repairs cerebral neovascularisation in diabetes...
April 2017: Diabetologia
https://www.readbyqxmd.com/read/28101124/reduced-up-regulation-of-the-nitric-oxide-pathway-and-impaired-endothelial-and-smooth-muscle-functions-in-the-female-type-2-diabetic-goto-kakizaki-rat-heart
#16
Martine Desrois, Carole Lan, Jamileh Movassat, Monique Bernard
BACKGROUND: Type 2 diabetes is associated with greater relative risk of cardiovascular diseases in women than in men, which is not well understood. Consequently, we have investigated if male and female displayed differences in cardiac function, energy metabolism, and endothelial function which could contribute to increased cardiovascular complications in type 2 diabetic female. METHODS: Male and female Control and type 2 diabetic Goto-Kakizaki (GK) isolated rat hearts were perfused during 28 min with a physiological buffer before freeze-clamping for biochemical assays...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28042873/a-mini-network-balance-model-for-evaluating-the-progression-of-cardiovascular-complications-in-goto-kakizaki-rats
#17
Hao Jiang, Yu-Hao Wang, Chun-Xiang Wei, Xue Zhang, Hao-Chen Liu, Xiao-Quan Liu
Cardiovascular complications represent a leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). During such complicated progression, subtle variations in the cardiovascular risk (CVR)-related biomarkers have been used to identify cardiovascular disease at the incipient stage. In this study we attempt to integrally characterize the progression of cardiovascular complications and to assess the beneficial effects of metformin combined with salvianolic acid A (Sal A), in Goto-Kakizaki (GK) rats with spontaneous T2DM...
March 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27982676/lipasin-betatrophin-is-differentially-expressed-in-liver-and-white-adipose-tissue-without-association-with-insulin-resistance-in-wistar-and-goto-kakizaki-rats
#18
M Cahová, D Habart, T Olejár, Z Berková, Z Papáčková, H Daňková, A Lodererova, M Heczková, F Saudek
Lipasin is a recently identified lipokine expressed predominantly in liver and in adipose tissue. It was linked to insulin resistance in mice and to type 1 and type 2 diabetes (T1D, T2D) in humans. No metabolic studies concerning lipasin were performed yet in rats. Therefore, we used rat model of T2D and insulin resistance, Goto-Kakizaki (GK) rats, to determine changes of lipasin expression in liver and in white adipose tissue (WAT) over 52 weeks in the relation to glucose tolerance, peripheral tissue insulin sensitivity and adiposity...
May 4, 2017: Physiological Research
https://www.readbyqxmd.com/read/27904691/implantation-of-placenta-derived-mesenchymal-stem-cells-accelerates-murine-dermal-wound-closure-through-immunomodulation
#19
Haifeng Wang, Lianyu Chen, Yang Liu, Bangzhen Luo, Nanzi Xie, Tao Tan, Lige Song, Pei Erli, Ming Luo
BACKGROUND: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus. Although previous studies have established that inflammation, ischemia and neuropathy contribute to the development of DFU, it is still an unmet medical need due to lack knowledge of cellular and molecular mechanisms associated with DFU. In the present study, we tested our hypothesis that subcutaneous application of human placental mesenchymal stem cells (PMSCs) can accelerate diabetic dermal wound healing by modulating immunoresponse...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27881924/rodent-models-of-diabetic-nephropathy-their-utility-and-limitations
#20
REVIEW
Munehiro Kitada, Yoshio Ogura, Daisuke Koya
Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes...
2016: International Journal of Nephrology and Renovascular Disease
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