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https://www.readbyqxmd.com/read/28805979/effects-of-mtor-inhibition-on-cardiac-and-adipose-tissue-pathology-and-glucose-metabolism-in-rats-with-metabolic-syndrome
#1
Ayako Uchinaka, Mamoru Yoneda, Yuichiro Yamada, Toyoaki Murohara, Kohzo Nagata
The mammalian target of rapamycin (mTOR) is a regulator of metabolism and is implicated in pathological conditions such as obesity and diabetes. We aimed to investigate the role of mTOR in obesity. A new animal model of metabolic syndrome (MetS), named DahlS.Z-Lepr(fa) /Lepr(fa) (DS/obese) rats was established previously in our laboratory. In this study, we used this model to evaluate the effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism. DS/obese rats were treated with the mTOR inhibitor, everolimus, (0...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28805970/a-novel-free-fatty-acid-receptor-1-gpr40-ffar1-agonist-mr1704-enhances-glucose-dependent-insulin-secretion-and-improves-glucose-homeostasis-in-rats
#2
Naoto Tsuda, Atsuko Kawaji, Toshihiro Sato, Mitsuhiro Takagi, Chika Higashi, Yutaka Kato, Kumiko Ogawa, Hiroyasu Naba, Munetaka Ohkouchi, Masaki Nakamura, Yoshitaka Hosaka, Junichi Sakaki
Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats. Treatment of rat islets with MR1704 increased glucose-dependent insulin secretion...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28801532/activation-of-nkx2-5-calr-p53-signaling-pathway-by-hyperglycemia-induces-cardiac-remodeling-and-dysfunction-in-adult-zebrafish
#3
Sun Yanyi, Wang Qiuyun, Fang Yuehua, Wu Chunfang, Lu Guoping, Chen Zhenyue
Hyperglycemia is an independent risk factor for diabetic cardiomyopathy in humans; however, the underlying mechanisms have not been thoroughly elucidated. Zebrafish (Danio rerio) was used in this study as a novel vertebrate model to explore the signaling pathways of human adult cardiomyopathy. Hyperglycemia was induced by alternately immersing adult zebrafish in a glucose solution or water. The hyperglycemic fish gradually exhibited some hallmarks of cardiomyopathy such as myocardial hypertrophy and apoptosis, myofibril loss, fetal gene reactivation, and severe arrhythmia...
August 11, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28800677/levothyroxine-enhances-glucose-clearance-and-blunts-the-onset-of-experimental-type-1-diabetes-mellitus-in-mice
#4
Livia López-Noriega, Nadia Cobo-Vuilleumier, Álvaro Jesús Narbona-Pérez, Juan Luis Araujo-Garrido, Petra Isabel Lorenzo, José Manuel Mellado-Gil, José Carlos Moreno, Benoit R Gauthier, Alejandro Martín-Montalvo
BACKGROUND AND PURPOSE: Thyroid hormones induce several changes in whole body metabolism that are known to improve metabolic homeostasis. However, adverse side effects have prevented its use in the clinic. In view of the promising effects of thyroid hormones, we investigated the effects of levothyroxine supplementation in glucose. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with levothyroxine from birth to 24 weeks of age, when mice were euthanized. The effects of levothyroxine supplementation on metabolic health were determined...
August 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28799229/sitagliptin-mediated-preservation-of-endothelial-progenitor-cell-function-via-augmenting-autophagy-enhances-ischaemic-angiogenesis-in-diabetes
#5
Xiaozhen Dai, Jun Zeng, Xiaoqing Yan, Qian Lin, Kai Wang, Jing Chen, Feixia Shen, Xuemei Gu, Yuehui Wang, Jun Chen, Kejian Pan, Lu Cai, Kupper A Wintergerst, Yi Tan
Recently, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin, a major anti-hyperglycaemic agent, has received substantial attention as a therapeutic target for cardiovascular diseases via enhancing the number of circulating endothelial progenitor cells (EPCs). However, the direct effects of sitagliptin on EPC function remain elusive. In this study, we evaluated the proangiogenic effects of sitagliptin on a diabetic hind limb ischaemia (HLI) model in vivo and on EPC culture in vitro. Treatment of db/db mice with sitagliptin (Januvia) after HLI surgery efficiently enhanced ischaemic angiogenesis and blood perfusion, which was accompanied by significant increases in circulating EPC numbers...
August 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28799221/repose-repositioning-insulin-pump-therapy-in-type-1-diabetes
#6
N S Oliver
In 2008, the National Institute for Health and Care Excellence (NICE) technology appraisal of continuous subcutaneous insulin infusion (CSII, insulin pump therapy) for people with Type 1 diabetes was published [1]. Implementation of this enables children under the age of 12 years to access CSII, and consideration of CSII for adults and children over 12 years with challenging hypo- or hyperglycaemia. In Scotland, the Scottish Intercollegiate Guidelines Network (SIGN) guidance for management of diabetes states that CSII therapy should be considered for people unable to achieve their glycaemic targets, for those who experience recurring episodes of severe hypoglycaemia, and in infants and very young children with very low basal insulin requirements, for whom even small doses of basal insulin analogue may result in hypoglycaemia [2]...
August 11, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28797248/the-role-of-bariatric-surgery-to-treat-diabetes-current-challenges-and-perspectives
#7
REVIEW
Chrysi Koliaki, Stavros Liatis, Carel W le Roux, Alexander Kokkinos
Bariatric surgery is emerging as a powerful weapon against severe obesity and type 2 diabetes mellitus (T2DM). Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to treat T2DM, especially in light of accumulating evidence that surgery with gastrointestinal manipulations may result in T2DM remission (metabolic surgery). The major mechanisms mediating the weight loss-independent effects of bariatric surgery comprise effects on tissue-specific insulin sensitivity, β-cell function and incretin responses, changes in bile acid composition and flow, modifications of gut microbiota, intestinal glucose metabolism and increased brown adipose tissue metabolic activity...
August 10, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28794898/a-multicenter-cohort-study-of-primary-hypertension-in-korea-study-design-and-interim-analysis-of-the-korean-registry-of-target-organ-damage-in-hypertension-korhr
#8
Suk-Won Choi, Seong Woo Han, Jong Sun Ok, Byung-Su Yoo, Mi-Seung Shin, Sung Ha Park, Kyu-Hyung Ryu
BACKGROUND: The Korean Registry of Target Organ Damage in Hypertension aims to evaluate the clinical characteristics and prevalence of subclinical target organ damage in Korean hypertensive patients. METHOD: This is a prospective, observational, multicenter cohort study in which 23 university hospitals participated. Since May 2013, we have enrolled 1,318 consecutive hypertensive patients without known cardiovascular disease who met the following inclusion criteria: 1) age older than 30 years and 2) the first visit to the participating hospitals was within the last 5 years...
2017: Clinical Hypertension
https://www.readbyqxmd.com/read/28790859/dyslipidemia-and-associated-factors-among-diabetic-patients-attending-durame-general-hospital-in-southern-nations-nationalities-and-people-s-region
#9
Shiferaw Bekele, Tagesech Yohannes, Abdurehman Eshete Mohammed
BACKGROUND: Diabetes mellitus is a group of metabolic disorders that are caused by deficiency in insulin secretion or the decreased ability of insulin to act effectively on target tissues, particularly muscle, liver, and fat. As a result of insulin resistance in the target tissues, particularly in the adipocytes, free fatty acid flux is increased, leading to increased lipid synthesis in hepatocytes, which is responsible for diabetic dyslipidemia. OBJECTIVE: The objective of this study was to determine the prevalence and associated factors of dyslipidemia among diabetic patients in Durame General Hospital in Kembata Tembaro zone...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28782823/drugs-and-the-kidneys-clinical-pharmacology-perspectives
#10
EDITORIAL
John Vincent
The focus of this edition of Clinical Pharmacolgoy & Therapeutics (CPT) is on drugs and renal function and will not include a detailed discussion of kidney disease and its treatment. It is well recognized that drugs affect the kidneys in different ways, while kidney disease impacts drug metabolism and response. It is impossible to underestimate the value of the kidneys to man in health and disease, from regulation of fluid and electrolyte balance to participating in drug metabolism and transport. Additionally, the kidneys serve as targets for drugs used to treat cardiovascular (CV) diseases including hypertension and heart failure, metabolic diseases such as diabetes mellitus and obesity, chronic kidney disease (CKD), as well as playing a role in the regulation of several hormones...
September 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28780379/proinflammatory-cytokine-mif-plays-a-role-in-the-pathogenesis-of-type-2-diabetes-mellitus-but-does-not-affect-hepatic-mitochondrial-function
#11
Miriam Rodriguez-Sosa, Tecilli Cabellos-Avelar, Yuriko Sanchez-Zamora, Imelda Juárez-Avelar, Esperanza García-Reyes, Alejandra Lira-León, José Del Carmen Benítez-Flores, Thalia Pacheco-Fernández, Marcia Hiriart, Emma Berta Gutiérrez-Cirlos
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). Although the effect of high glucose on liver function has been described, the role of MIF in hepatic mitochondrial function during T2DM has not been studied. OBJECTIVE: We examine the influence of MIF to hepatic mitochondrial function in T2DM mouse model. METHODS: WT and Mif(-/-) BALB/c mice were treated with a single dose of streptozotocin (STZ)...
August 2, 2017: Cytokine
https://www.readbyqxmd.com/read/28776185/modulation-of-cellular-energetics-by-galactose-and-pioglitazone
#12
David Grimm, Leonardo Altamirano, Sudip Paudel, Leah Welker, Mary E Konkle, Nilay Chakraborty, Michael A Menze
The Warburg effect is ameliorated by culturing transformed cells in the presence of galactose instead of glucose as the primary carbon source. However, metabolic consequences may occur in addition to sensitizing the cells to mitochondrial toxins. The screening of pharmaceutical agents against transformed cells while using galactose must therefore be carefully evaluated. Pioglitazone is employed in clinical applications to treat type-2 diabetes but clearly has other off-target effects. Human hepatocellular carcinoma cells (HepG2) were cultured in glucose or galactose-containing medium to investigate the role of pioglitazone on cellular bioenergetics by calorimetry and respirometry...
August 3, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28774917/targeting-an-energy-sensor-to-treat-diabetes
#13
D Grahame Hardie
No abstract text is available yet for this article.
August 4, 2017: Science
https://www.readbyqxmd.com/read/28774208/moving-beyond-subcutaneous-insulin-the-application-of-adjunctive-therapies-to-the-treatment-of-type-1-diabetes
#14
Kathleen H Ang, Jennifer L Sherr
With the discovery of insulin nearly a century ago, the diagnosis of Type 1 Diabetes (T1D) transformed from a death sentence to a chronic medical condition. Despite the advances that have been made, the vast majority of those living with T1D still struggle to achieve targeted control. Yet, a plethora of agents have been developed to treat those with Type 2 Diabetes. Exploration of how these agents may benefit those with T1D has been an area of intense investigation, especially due to the overweight/obesity epidemic, which now afflicts more than 60% of those living with T1D...
August 3, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28770542/process-based-treatment-of-diabetes-in-kaiser-permanente-southern-california-how-to-make-diabetes-care-complete
#15
REVIEW
John P Martin, Natalie Aboubechara
PURPOSE OF REVIEW: The purpose of this review was to provide an overview of the Kaiser Permanente Southern California (KPSC) Complete Care management strategy. RECENT FINDINGS: The KPSC Complete Care program allows members of care management teams to coordinate the administration of care for patients with diabetes. This program encompasses teams of physicians, physician assistants, pharmacists, nurse practitioners, registered nurse (RN) care managers, office-based RNs, health educators, and many others to contribute to the glycemic and overall health outcomes for our patients with diabetes...
September 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28769873/targeting-obesity-and-diabetes-to-treat-heart-failure-with-preserved-ejection-fraction
#16
REVIEW
Raffaele Altara, Mauro Giordano, Einar S Nordén, Alessandro Cataliotti, Mazen Kurdi, Saeed N Bajestani, George W Booz
Heart failure with preserved ejection fraction (HFpEF) is a major unmet medical need that is characterized by the presence of multiple cardiovascular and non-cardiovascular comorbidities. Foremost among these comorbidities are obesity and diabetes, which are not only risk factors for the development of HFpEF, but worsen symptoms and outcome. Coronary microvascular inflammation with endothelial dysfunction is a common denominator among HFpEF, obesity, and diabetes that likely explains at least in part the etiology of HFpEF and its synergistic relationship with obesity and diabetes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28765738/baseline-characteristics-of-a-retrospective-patient-cohort-in-the-korean-vascular-intervention-society-endovascular-therapy-in-lower-limb-artery-diseases-k-vis-ella-registry
#17
Young-Guk Ko, Chul-Min Ahn, Pil-Ki Min, Jae-Hwan Lee, Chang-Hwan Yoon, Cheol Woong Yu, Seung Whan Lee, Sang-Rok Lee, Seung Hyuk Choi, Yoon Seok Koh, In-Ho Chae, Donghoon Choi
BACKGROUND AND OBJECTIVES: The Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases (K-VIS ELLA) Registry is a multicenter observational study with retrospective and prospective cohorts of patients with lower extremity peripheral artery disease (PAD) undergoing endovascular treatment. In this study, we report the baseline characteristics of this retrospective cohort. SUBJECTS AND METHODS: In the present study we analyzed datasets of 3073 patients with 3972 target limbs from a retrospective cohort treated with endovascular therapy in 31 Korean hospitals...
July 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/28765731/combining-potent-statin-therapy-with-other-drugs-to-optimize-simultaneous-cardiovascular-and-metabolic-benefits-while-minimizing-adverse-events
#18
REVIEW
Kwang Kon Koh, Ichiro Sakuma, Kazunori Shimada, Toshio Hayashi, Michael J Quon
Hypercholesterolemia and hypertension are among the most important risk factors for cardiovascular (CV) disease. They are also important contributors to metabolic diseases including diabetes that further increase CV risk. Updated guidelines emphasize targeted reduction of overall CV risks but do not explicitly incorporate potential adverse metabolic outcomes that also influence CV health. Hypercholesterolemia and hypertension have synergistic deleterious effects on interrelated insulin resistance and endothelial dysfunction...
July 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/28763121/proportion-of-daily-capillary-blood-glucose-readings-required-in-the-target-range-for-target-glycaemic-control-shift-of-focus-from-target-range-to-proportion-in-range
#19
S Sivasubramaniyam, S Amiel, P Choudhary
AIM: Most guidelines provide people with Type 1 diabetes with pre- and post-meal capillary blood glucose (CBG) targets to achieve optimal glycaemic control. We evaluated the proportion of daily CBG readings between 4 and 10 mmol/l in people achieving different HbA1c levels. METHOD: We analysed CBG data from routine pump/meter downloads from 201 adults treated with continuous subcutaneous insulin infusion (CSII) at a single hospital clinic. Exclusion criteria were CSII < 6 months, < 3 CBG/day, pregnancy, haemoglobinopathy and continuous sensor use...
August 1, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28762248/engineering-brown-fat-into-skeletal-muscle-using-ultrasound-targeted-microbubble-destruction-gene-delivery-in-obese-zucker-rats-proof-of-concept-design
#20
Raul A Bastarrachea, Jiaxi Chen, Jack W Kent, Edna J Nava-Gonzalez, Ernesto Rodriguez-Ayala, Marcel M Daadi, Barbara Jorge, Hugo Laviada-Molina, Anthony G Comuzzie, Shuyuan Chen, Paul A Grayburn
Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue-specific gene delivery. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice...
July 31, 2017: IUBMB Life
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