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https://www.readbyqxmd.com/read/28549111/diabetic-db-db-mice-do-not-develop-heart-failure-upon-pressure-overload-a-longitudinal-in-vivo-pet-mri-and-mrs-study-on-cardiac-metabolic-structural-and-functional-adaptations
#1
Desiree Abdurrachim, Miranda Nabben, Verena Hoerr, Michael T Kuhlmann, Philipp Bovenkamp, Jolita Ciapaite, Ilvy M E Geraets, Will Coumans, Joost J F P Luiken, Jan F C Glatz, Michael Schäfers, Klaas Nicolay, Cornelius Faber, Sven Hermann, Jeanine J Prompers
Aim: Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Methods and results: Transverse aortic constriction (TAC) was performed in non-diabetic ( db /+) and diabetic ( db/db ) mice to induce pressure overload...
May 26, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28542610/gpr40-partial-agonist-mk-2305-lower-fasting-glucose-in-the-goto-kakizaki-rat-via-suppression-of-endogenous-glucose-production
#2
Corin Miller, Michele J Pachanski, Melissa E Kirkland, Daniel T Kosinski, Joel Mane, Michelle Bunzel, Jin Cao, Sarah Souza, Brande Thomas-Fowlkes, Jerry Di Salvo, Adam B Weinglass, Xiaoyan Li, Robert W Myers, Kevin Knagge, Paul E Carrington, William K Hagmann, Maria E Trujillo
GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40 partial agonists improve glucose homeostasis, we evaluated the effects of MK-2305, a potent and selective partial GPR40 agonist, in diabetic Goto Kakizaki rats. MK-2305 decreased fasting glucose after acute and chronic treatment. MK-2305-mediated changes in glucose were coupled with increases in plasma insulin during hyperglycemia and glucose challenges but not during fasting, when glucose was normalized...
2017: PloS One
https://www.readbyqxmd.com/read/28542422/angelica-dahurica-ethanolic-extract-improves-impaired-wound-healing-by-activating-angiogenesis-in-diabetes
#3
Xiao-Na Zhang, Ze-Jun Ma, Ying Wang, Bei Sun, Xin Guo, Cong-Qing Pan, Li-Ming Chen
Abnormal angiogenesis plays an important role in impaired wound healing and development of chronic wounds in diabetes mellitus. Angelica dahurica radix is a common traditional Chinese medicine with wide spectrum medicinal effects. In this study, we analyzed the potential roles of Angelica dahurica ethanolic extract (ADEE) in correcting impaired angiogenesis and delayed wound healing in diabetes by using streptozotocin-induced diabetic rats. ADEE treatment accelerated diabetic wound healing through inducing angiogenesis and granulation tissue formation...
2017: PloS One
https://www.readbyqxmd.com/read/28539272/selenium-nanoparticles-as-versatile-carriers-for-oral-delivery-of-insulin-insight-into-the-synergic-antidiabetic-effect-and-mechanism
#4
Wenji Deng, Qian Xie, Huan Wang, Zhiguo Ma, Baojian Wu, Xingwang Zhang
Oral insulin delivery has been plagued by limited bioavailability. This work reports selenium nanoparticles (SeNPs) for oral insulin delivery to overcome the absorption barrier. Insulin-loaded SeNPs (INS-SeNPs) were fabricated by ionic cross-linking/in situ reduction and characterized by particle size and drug entrapment. The resultant INS-SeNPs were 120nm around in particle size with high drug loading. INS-SeNPs exhibited controllable insulin release and outstanding stability in the digestive fluids. INS-SeNPs caused a significant hypoglycemic effect in both normal and diabetic rats...
May 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28533437/metformin-inhibits-cellular-proliferation-and-bioenergetics-in-colorectal-cancer-patient-derived-xenografts
#5
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing pre-clinical evidence suggesting that metformin, an anti-diabetic drug, has anti-cancer properties against various malignancies including colorectal cancer (CRC). However, majority of evidence which were derived from cancer cell lines and xenografts are likely to overestimate the benefit of metformin since these models are inadequate and require supraphysiological levels of metformin. Here, we generated patient-derived xenografts (PDX) lines from 2 CRC patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for CRC...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28506456/prevalence-of-asymptomatic-coronary-heart-disease-in-the-siblings-of-young-myocardial-infarction-patients-as-detected-by-coronary-computer-tomography-angiography-a-pilot-study
#6
Nadim Shah, Chiew Wong, Nicholas Cox, Anne-Maree Kelly, Kean Soon
BACKGROUND: There is little data on the prevalence of coronary heart disease (CHD) in the young. The study aimed to estimate the prevalence of asymptomatic CHD in siblings of young patients with myocardial infarction (MI) using coronary computed tomography angiography (CCTA). METHODS: Prospective observational data was collected on siblings of patients aged ≤55 years presenting with acute MI and having coronary stenosis ≥50% on invasive coronary angiography in at least one epicardial coronary artery...
April 27, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28487436/protective-effect-of-let-7-mirna-family-in-regulating-inflammation-in-diabetes-associated-atherosclerosis
#7
Eoin Brennan, Bo Wang, Aaron McClelland, Muthukumar Mohan, Mariam Marai, Ophelie Beuscart, Sinda Derouiche, Stephen Gray, Raelene Pickering, Chris Tikellis, Monica de Gaetano, Mary Barry, Orina Belton, Syed Tasadaque Ali-Shah, Patrick Guiry, Karin Am Jandeleit-Dahm, Mark E Cooper, Catherine Godson, Phillip Kantharidis
The let-7 miRNA family play a key role in modulating inflammatory responses. Vascular smooth muscle cell (SMC) proliferation, and endothelial cell (EC) dysfunction are critical in the pathogenesis of atherosclerosis, including in the setting of diabetes. Here we report that let-7 levels are decreased in diabetic human carotid plaques and in a model of diabetes-associated atherosclerosis (DAA), the diabetic ApoE(-/-) mouse. In vitro, platelet-derived growth factor (PDGF) and tumor necrosis factor-alpha (TNF-α) induced vascular SMC and EC activation was associated with reduced let-7 miRNA expression, via Lin28b, a negative regulator of let-7 biogenesis...
May 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28487104/sugar-sweetened-beverages-consumption-is-associated-with-abdominal-obesity-risk-in-diabetic-patients
#8
Razieh Anari, Reza Amani, Masoud Veissi
AIM: Sugar sweetened beverages (SSBs) are any beverages containing added-sugar and supposed to increase body lipogenesis and fat accumulation in healthy subjects. This study was performed to assess the possible association between SSBs consumption and obesity in type 2 diabetes (T2DM) patients. METHODS: T2DM adults with no insulin treatment entered the study. Abdominal obesity and general adiposity were determined using waist circumference (WC) and body mass index (BMI), respectively...
April 28, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28483629/dialkylcarbamoyl-chloride-dressings-in-the-prevention-of-surgical-site-infections-following-non-implant-vascular-surgery
#9
Nelson Bua, George E Smith, Joshua P Totty, Daniel Pan, Tom Wallace, Daniel Carradice, Ian C Chetter
BACKGROUND: Dressings coated with Dialkylcarbamoyl chloride (DACC) are highly hydrophobic and irreversibly bind multiple types of bacteria, trapping them in the dressing and reducing the number of organisms at the wound surface. We aimed to assess the impact of DACC coated postoperative dressings on the incidence of surgical site infection (SSI) in non-implant vascular surgery patients. METHODS: Two hundred patients undergoing non implant vascular surgery were prospectively recruited at a single vascular centre...
May 5, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28465284/development-of-diabetes-does-not-alter-behavioral-and-molecular-circadian-rhythms-in-a-transgenic-rat-model-of-type-2-diabetes-mellitus
#10
Jingyi Qian, Anthony P Thomas, Analyne M Schroeder, Kuntol Rakshit, Christopher S Colwell, Aleksey V Matveyenko
Metabolic state and circadian clock function exhibit complex bidirectional relationship. Circadian disruption increases propensity for metabolic dysfunction, whereas common metabolic disorders such as obesity and Type 2 diabetes (T2DM) are associated with impaired circadian rhythms. Specifically, alterations in glucose availability and glucose metabolism have been shown to modulate clock gene expression and function in vitro; however to date it is unknown whether development of diabetes imparts deleterious effects on the suprachiasmatic nucleus (SCN) circadian clock and SCN-driven outputs in vivo...
May 2, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28465178/oral-delivery-of-ursolic-acid-loaded-nanostructured-lipid-carrier-coated-with-chitosan-oligosaccharides-development-characterization-in-vitro-and-in-vivo-assessment-for-the-therapy-of-leishmaniasis
#11
Suman Das, Santanu Ghosh, Asit Kumar De, Tanmoy Bera
Visceral leishmaniasis (VL) is a life-threatening disease caused by Leishmania donovani due to uncontrolled parasitisation of liver, spleen, and bone marrow. Ursolic acid (UA), a promising anti-inflammatory, anti-bacterial and anti-diabetic drug used successfully for treatment of ailments. Development of new delivery system is extremely urgent for UA with better efficacy and fewer side effects. The aim of present research work was to formulate and evaluate the potential anti-leishmanial activity of UA loaded N-octyl-chitosan surface decorated nanostructured lipid carrier system (UA-NLC) for delivery to the macrophages for VL...
April 29, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28461456/elovl6-deficiency-improves-glycemic-control-in-diabetic-db-db-mice-by-expanding-%C3%AE-cell-mass-and-increasing-insulin-secretory-capacity
#12
Hui Zhao, Takashi Matsuzaka, Yuta Nakano, Kaori Motomura, Nie Tang, Tomotaka Yokoo, Yuka Okajima, Song-Iee Han, Yoshinori Takeuchi, Yuichi Aita, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Hirohito Sone, Nobuhiro Yamada, Hitoshi Shimano
Dysfunctional fatty acid (FA) metabolism plays an important role in the pathogenesis of β-cell dysfunction and loss of β-cell mass in type 2 diabetes (T2D). Elovl6 is a microsomal enzyme that is responsible for converting C16 saturated and monounsaturated FAs into C18 species. We previously showed that Elovl6 played a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further define its role in T2D development, we assessed the effects of Elovl6 deletion in leptin receptor-deficient C57BL/KsJ db/db mice, a model of T2D...
May 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28460190/exercise-improves-femoral-whole-bone-and-tissue-level-biomechanical-properties-in-hyperphagic-oletf-rats
#13
Laura C Ortinau, Melissa A Linden, R Scott Rector, Pamela S Hinton
An often-overlooked comorbidity of type 2 diabetes (T2D) is increased fracture risk. Since traditional T2D therapies focus solely on glucose homeostasis, there is an increased need for effective treatment strategies that improve both metabolic and bone health. The current study evaluated if previously reported protective effects of exercise (EX) on cortical bone geometry and biomechanical properties are due to the prevention of obesity compared to obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats or the unique skeletal effects of exercise...
May 1, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28452143/zy15557-a-novel-long-acting-dpp-4-inhibitor-for-the-treatment-of-type-2-diabetes-mellitus
#14
M R Jain, A A Joharapurkar, S G Kshirsagar, V J Patel, R H Bahekar, H V Patel, P A Jadav, P R Patel, R C Desai
BACKGROUND AND PURPOSE: Dipeptidylpeptidase 4 (DPP-4) inhibitors increase levels of glucagon-like peptide -1 (GLP-1) and provide clinical benefit in the treatment of type 2 diabetes mellitus. Since longer acting inhibitors have therapeutic advantage, we developed a novel DPP-4 inhibitor, ZY15557 that has a sustained action and long half-life. EXPERIMENTAL APPROACH: We studied the potency, selectivity, efficacy and duration of action of ZY15557 using in vitro and in vivo preclinical models...
April 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28445787/adipose-derived-stem-cells-were-impaired-in-restricting-cd4-t-cell-proliferation-and-polarization-in-type-2-diabetic-apoe-mouse
#15
Ming-Hao Liu, Ya Li, Lu Han, Yao-Yuan Zhang, Di Wang, Zhi-Hao Wang, Hui-Min Zhou, Ming Song, Yi-Hui Li, Meng-Xiong Tang, Wei Zhang, Ming Zhong
BACKGROUND: Atherosclerosis (AS) is the most common and serious complication of type 2 diabetes mellitus (T2DM) and is accelerated via chronic systemic inflammation rather than hyperglycemia. Adipose tissue is the major source of systemic inflammation in abnormal metabolic state. Pro-inflammatory CD4(+)T cells play pivotal role in promoting adipose inflammation. Adipose-derived stem cells (ADSCs) for fat regeneration have potent ability of immunosuppression and restricting CD4(+)T cells as well...
April 23, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28439523/tsallis-entropy-and-sparse-reconstructive-dictionary-learning-for-exudate-detection-in-diabetic-retinopathy
#16
Vineeta Das, Niladri B Puhan
Computer-assisted automated exudate detection is crucial for large-scale screening of diabetic retinopathy (DR). The motivation of this work is robust and accurate detection of low contrast and isolated hard exudates using fundus imaging. Gabor filtering is first performed to enhance exudate visibility followed by Tsallis entropy thresholding. The obtained candidate exudate pixel map is useful for further removal of falsely detected candidates using sparse-based dictionary learning and classification. Two reconstructive dictionaries are learnt using the intensity, gradient, local energy, and transform domain features extracted from exudate and background patches of the training fundus images...
April 2017: Journal of Medical Imaging
https://www.readbyqxmd.com/read/28435237/evaluation-of-ex-press-glaucoma-implant-in-elderly-diabetic-patients-after-23g-vitrectomy
#17
Anita Lyssek-Boroń, Adam Wylęgała, Dariusz Dobrowolski, Ewelina Kowalczyk, Katarzyna Polanowska, Edward Wylęgała
PURPOSE: The most frequent qualifications for pars plana vitrectomy (PPV) in diabetic patients include recurrent hemorrhage into the vitreous body chamber and vitreoretinal proliferation, also with traction retinal detachment. The aim of this study was to evaluate the effectiveness of EX-PRESS implant for the treatment of secondary glaucoma in elderly diabetic patients following PPV 23G with silicon oil or SF6 gas endotamponade. MATERIALS AND METHODS: This retrospective analysis comprised 18 patients (19 eyes)...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28435021/the-mtorc2-pkc-pathway-sustains-compensatory-insulin-secretion-of-pancreatic-%C3%AE-cells-in-response-to-metabolic-stress
#18
Yun Xie, Canqi Cui, Aifang Nie, Yan Wang, Qicheng Ni, Yun Liu, Qinglei Yin, Hongli Zhang, Yong Li, Qidi Wang, Yanyun Gu, Guang Ning
BACKGROUND: Compensation of the pancreatic β cell functional mass in response to metabolic stress is key to the pathogenesis of Type 2 Diabetes. The mTORC2 pathway governs fuel metabolism and β cell functional mass. It is unknown whether mTORC2 is required for regulating metabolic stress-induced β cell compensation. METHODS: We challenged four-week-old β-cell-specific Rictor (a key component of mTORC2)-knockout mice with a high fat diet (HFD) for 4weeks and measured metabolic and pancreatic morphological parameters...
April 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28433543/phenformin-inhibits-myeloid-derived-suppressor-cells-and-enhances-the-anti-tumor-activity-of-pd-1-blockade-in-melanoma
#19
Sun Hye Kim, Man Li, Sebastian Trousil, Yaqing Zhang, Marina Pasca di Magliano, Kenneth D Swanson, Bin Zheng
Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells (G-MDSCs) in spleens of tumor bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in G-MDSC, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28425952/antioxidant-and-anti-senescence-effect-of-metformin-on-mouse-olfactory-ensheathing-cells-moecs-may-be-associated-with-increased-brain-derived-neurotrophic-factor-levels-an-ex-vivo-study
#20
Agnieszka Śmieszek, Zuzanna Stręk, Katarzyna Kornicka, Jakub Grzesiak, Christine Weiss, Krzysztof Marycz
Metformin, the popular anti-diabetic drug was shown to exert multiple biological effects. The most recent metformin gained attention as an agent that mobilizes endogenous progenitor cells and enhances regenerative potential of organisms, for example by promoting neurogenesis. In the present study, we examined the role of metformin on mouse olfactory ensheathing cells (mOECs) derived from animals receiving metformin for eight weeks at a concentration equal to 2.8 mg/day. The mOECs expanded ex vivo were characterized in terms of their cellular phenotype, morphology, proliferative activity, viability and accumulation of oxidative stress factors...
April 20, 2017: International Journal of Molecular Sciences
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