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https://www.readbyqxmd.com/read/29779018/common-and-unique-transcriptional-responses-to-dietary-restriction-and-loss-of-insulin-receptor-substrate-1-irs1-in-mice
#1
Melissa M Page, Eugene F Schuster, Manikhandan Mudaliar, Pawel Herzyk, Dominic J Withers, Colin Selman
Dietary restriction (DR) is the most widely studied non-genetic intervention capable of extending lifespan across multiple taxa. Modulation of genes, primarily within the insulin/insulin-like growth factor signalling (IIS) and the mechanistic target of rapamycin (mTOR) signalling pathways also act to extend lifespan in model organisms. For example, mice lacking insulin receptor substrate-1 (IRS1) are long-lived and protected against several age-associated pathologies. However, it remains unclear how these particular interventions act mechanistically to produce their beneficial effects...
May 20, 2018: Aging
https://www.readbyqxmd.com/read/29777919/brain-to-bone-what-is-the-contribution-of-the-brain-to-skeletal-homeostasis
#2
REVIEW
Anna Idelevich, Roland Baron
The brain, which governs most, if not all, physiological functions in the body, from the complexities of cognition, learning and memory, to the regulation of basal body temperature, heart rate and breathing, has long been known to affect skeletal health. In particular, the hypothalamus - located at the base of the brain in close proximity to the medial eminence, where the blood-brain-barrier is not as tight as in other regions of the brain but rather "leaky", due to fenestrated capillaries - is exposed to a variety of circulating body cues, such as nutrients (glucose, fatty acids, amino acids), and hormones (insulin, glucagon, leptin, adiponectin) [1-3]...
May 16, 2018: Bone
https://www.readbyqxmd.com/read/29777582/comparative-study-of-liraglutide-and-insulin-glargine-on-glycemic-control-and-pancreatic-%C3%AE-cell-function-in-db-db-mice
#3
Yanli Li, Jia Zheng, Yunfeng Shen, Wangen Li, Meimei Liu, Jun Wang, Surong Zhu, Meihua Wu
BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age...
May 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29777569/improving-metabolic-stability-with-deuterium-the-discovery-of-hwl-066-a-potent-and-long-acting-free-fatty-acid-receptor-1-agonists
#4
Chunxia Liu, Zheng Li, Wei Shi, Huilan Li, Nasi Wang, Yuxuan Dai, Chen Liao, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancing of glucose-stimulated insulin secretion. The FFA1 agonist GW9508 has great potential for the treatment of type 2 diabetes mellitus, but it has been suffering from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β-oxidation. To identify orally available analog without influence on the unique pharmacological mechanism of GW9508, we tried to interdict the metabolically labile group by incorporating two deuterium atoms at the α-position of phenylpropionic acid affording compound 4 (HWL-066)...
May 18, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29766791/immunometabolic-changes-in-hepatocytes-arising-from-obesity-and-the-practice-of-physical-exercise
#5
Paula Alves Monteiro, Wagner Prado, Thiago Ricardo Dos Santos Tenório, Luciane Magri Tomaz, David H St-Pierre, Fabio Santos Lira
Over the recent years, a particular interest was shown towards understanding the roles of excessive hepatic fat accumulation and the development of obesity-related diseases. While hepatic triacylglycerol accumulation seems to be a response to the systemic increase of insulin release, fatty acid metabolites contribute to the progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). It is widely accepted that NAFLD is a polygenic and multifactorial disease under the influence of critical behavioral factors such as overeating and sedentary lifestyles...
May 14, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29763559/long-acting-release-microspheres-containing-novel-glp-1-analog-as-an-antidiabetic-system
#6
Sida Ruan, Yuanyuan Gu, Bo Liu, Huashan Gao, Xiongwei Hu, Haiping Hao, Liang Jin, Ting Cai
Glucagon-like peptide 1 (GLP-1) has recently received significant attention as an efficacious way to treat diabetes mellitus. However, the short half-life of the peptide limits its clinical application in diabetes. In our previous study, a novel GLP-1 analog (PGLP-1) with a longer half-life was synthesized and evaluated. Herein, we prepared the PGLP-1-loaded poly(D,L-lactide-co- glycolide) microspheres to achieve long-term effects on blood glucose control. The incorporation of zinc ion into the formulation can effectively decrease the initial burst release, and a uniform drug distribution was obtained, in contrast to native PGLP-1 encapsulated microspheres...
May 15, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29745913/benefits-of-early-screening-and-proper-treatment-in-patient-with-significant-risk-factors-for-gestational-diabetes-mellitus-case-report
#7
V Limani
Gestational diabetes mellitus (GDM) occurs in 2-9% of all pregnancies. Evidence suggests that the use of insulin in treating hyperglycemia in GDM patients reduces the risk of perinatal morbidity. Pregnancy is an exciting time in a woman's life. However, once patient is diagnosed with GDM, she will be managed more intensively. GDM is managed using diet and exercise but one in six women with GDM requires insulin. A 35-year-old woman at the 14th gestational week of her tenth pregnancy was seen for routine prenatal care...
April 2018: Georgian Medical News
https://www.readbyqxmd.com/read/29743560/caspases-in-metabolic-disease-and-their-therapeutic-potential
#8
Claire H Wilson, Sharad Kumar
Caspases, a family of cysteine-dependent aspartate-specific proteases, are central to the maintenance of cellular and organismal homoeostasis by functioning as key mediators of the inflammatory response and/or apoptosis. Both metabolic inflammation and apoptosis play a central role in the pathogenesis of metabolic disease such as obesity and the progression of nonalcoholic steatohepatisis (NASH) to more severe liver disease. Obesity and nonalcoholic fatty liver disease (NAFLD) are the leading global health challenges associated with the development of numerous comorbidities including insulin resistance, type-2 diabetes and early mortality...
May 9, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29741925/glycemic-control-in-adult-type-1-diabetes-patients-with-insulin-glargine-insulin-detemir-or-continuous-subcutaneous-insulin-infusion-in-daily-practice
#9
Päivi Rautiainen, Hilkka Tirkkonen, Tiina Laatikainen
BACKGROUNDS: This study aims to compare glycemic control of persons with type 1 diabetes using multiple daily injections (MDI) with insulin glargine versus insulin detemir or with continuous subcutaneous insulin infusion (CSII) in daily practice. SUBJECTS AND METHODS: All adult individuals with type 1 diabetes (n = 1053) were identified from the electronic patient database in North Karelia, Finland. The persons' individual data for insulin treatment, diabetic ketoacidosis (DKA), and hemoglobin A1c (HbA1c) measurements during the year 2014 were obtained from medical records...
May 9, 2018: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/29731287/controversies-in-management-of-hyperkalemia
#10
Brit Long, Justin R Warix, Alex Koyfman
BACKGROUND: Hyperkalemia is a common electrolyte disorder that can result in morbidity and mortality if not managed appropriately. OBJECTIVES: This review evaluates the classic treatments of hyperkalemia and discusses controversies and new medications for management. DISCUSSION: Potassium (K+) plays a key role in determining the transmembrane potentials of "excitable membranes" present in nerve and muscle cells. K+ is the predominant intracellular cation, and clinical deterioration typically ensues when patients develop sufficiently marked elevation in extracellular fluid concentrations of K+ (hyperkalemia)...
May 3, 2018: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29709796/pharmacodynamics-and-pharmacokinetics-of-insulin-detemir-and-insulin-glargine-300-u-ml-in-healthy-dogs
#11
H Fink, C Herbert, C Gilor
Insulin glargine 300 U/mL and insulin detemir are synthetic long-acting insulin analogs associated with minimal day-to-day variability or episodes of hypoglycemia in people. Here, 8 healthy purpose-bred dogs each received 2.4 nmol/kg subcutaneous injections of insulin detemir (0.1 U/kg) and insulin glargine 300 U/mL (0.4 U/kg) on 2 different days, >1 wk apart, in random order. Blood glucose (BG) was measured every 5 min, and glucose was administered intravenously at a variable rate with the goal of maintaining BG within 10% of baseline BG ("isoglycemic clamp")...
April 10, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29704259/truss-exacerbates-nafld-development-by-promoting-i%C3%AE%C2%BAb%C3%AE-degradation
#12
Chang-Jiang Yu, Qiu-Shi Wang, Ming-Ming Wu, Bin-Lin Song, Chen Liang, Jie Lou, Liang-Liang Tang, Xiao-Di Yu, Na Niu, Xu Yang, Bao-Long Zhang, Yao Qu, Yang Liu, Zhi-Chao Dong, Zhi-Ren Zhang
There is no effective treatment method for non-alcoholic fatty liver disease (NAFLD), the most common liver disease. The exact mechanism underlying the pathogenesis of NAFLD remains to be elucidated. Here, we report that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS) acts as a positive regulator of NAFLD and in a variety of metabolic disorders. TRUSS expression was respectively increased in the human liver specimens with NAFLD or non-alcoholic steatohepatitis (NASH), and in the livers of high-fat diet (HFD)-induced and genetically obese (ob/ob) mice...
April 27, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29698923/anti-inflammatory-effects-of-%C3%AE-linolenic-acid-in-m1-like-macrophages-are-associated-with-enhanced-production-of-oxylipins-from-%C3%AE-linolenic-and-linoleic-acid
#13
Samantha D Pauls, Lisa A Rodway, Tanja Winter, Carla G Taylor, Peter Zahradka, Harold M Aukema
Chronic inflammation, mediated in large part by proinflammatory macrophage populations, contributes directly to the induction and perpetuation of metabolic diseases, including obesity, insulin resistance and type 2 diabetes. Polyunsaturated fatty acids (PUFAs) can have profound effects on inflammation through the formation of bioactive oxygenated metabolites called oxylipins. The objective of this study was to determine if exposure to the dietary omega-3 PUFA α-linolenic acid (ALA) can dampen the inflammatory properties of classically activated (M1-like) macrophages derived from the human THP-1 cell line and to examine the accompanying alterations in oxylipin secretion...
April 3, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29692257/current-views-on-dopaminergic-drugs-affecting-glucose-homeostasis
#14
Mortaza Fatehi Hassanabad, Mohammad Fatehi
BACKGROUND: For more than three decades, it has been known that manipulation of dopaminergic system could affect glucose homesotasis in experimental animals. The notion that glucose homeostasis in human might be influenced by dopaminergic drugs has attracted a great deal of attention in the past two decades. In spite of rapid advancements in revealing involvement of dopaminergic neurotransmission in insulin release, glucose up-take and pancreatic beta cell function in general through centrally and peripherally controlled mechanisms, there are discrepancies among observations on experimental animals and human subjects...
April 24, 2018: Current Diabetes Reviews
https://www.readbyqxmd.com/read/29688432/glucagonoma-with-necrolytic-migratory-erythema-metabolic-profile-and-detection-of-biallelic-inactivation-of-daxx-gene
#15
Ai Tamura, Tatsuki Ogasawara, Yoichi Fujii, Hiyori Kaneko, Akitoshi Nakayama, Seiichiro Higuchi, Naoko Hashimoto, Yui Miyabayashi, Masanori Fujimoto, Eri Komai, Takashi Kono, Ikki Sakuma, Hidekazu Nagano, Sawako Suzuki, Hisashi Koide, Koutaro Yokote, Kozue Iseki, Rena Oguma, Hiroyuki Matsue, Hiroyuki Nojima, Kensuke Sugiura, Hideyuki Yoshitomi, Masayuki Ohtsuka, Bahityar Rahmutulla, Atsushi Kaneda, Naoko Inoshita, Seishi Ogawa, Tomoaki Tanaka
Context: Necrolytic migratory erythema (NME) occurs in approximately 70% of patients with glucagonoma syndrome. Excessive stimulation of metabolic pathways by hyperglucagonemia, which leads to hypoaminoacidemia, contributes to NME pathogenesis. However, the molecular pathogenesis of glucagonoma and relationships between metabolic abnormalities and clinical symptoms remain unclear. Case description: A 53-year-old woman was referred to our hospital with a generalized rash and weight loss...
April 23, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29679004/the-linc01138-drives-malignancies-via-activating-arginine-methyltransferase-5-in-hepatocellular-carcinoma
#16
Zhe Li, Jiwei Zhang, Xinyang Liu, Shengli Li, Qifeng Wang, Di Chen, Zhixiang Hu, Tao Yu, Jie Ding, Jinjun Li, Ming Yao, Jia Fan, Shenglin Huang, Qiang Gao, Yingjun Zhao, Xianghuo He
Recurrent chromosomal aberrations have led to the discovery of oncogenes or tumour suppressors involved in carcinogenesis. Here we characterized an oncogenic long intergenic non-coding RNA in the frequent DNA-gain regions in hepatocellular carcinoma (HCC), LINC01138 (long intergenic non-coding RNA located on 1q21.2). The LINC01138 locus is frequently amplified in HCC; the LINC01138 transcript is stabilized by insulin like growth factor-2 mRNA-binding proteins 1/3 (IGF2BP1/IGF2BP3) and is associated with the malignant features and poor outcomes of HCC patients...
April 20, 2018: Nature Communications
https://www.readbyqxmd.com/read/29671202/pharmacokinetics-and-pharmacodynamics-of-once-weekly-somapacitan-in-children-and-adults-supporting-dosing-rationales-with-a-model-based-analysis-of-three-phase-i-trials
#17
Rasmus Vestergaard Juul, Michael Højby Rasmussen, Henrik Agersø, Rune Viig Overgaard
BACKGROUND: Somapacitan, a long-acting growth hormone (GH) derivative, has been well-tolerated in children with GH deficiency (GHD) and adults (healthy and adult GHD), in phase I, single- and multiple-dose trials, respectively, and has pharmacokinetic and pharmacodynamic properties supporting a once-weekly dosing regimen. OBJECTIVE: In the absence of a multiple-dose phase I trial in children with GHD, the aim was to develop a pharmacokinetic/pharmacodynamic model to predict somapacitan exposure and insulin-like growth factor-I (IGF-I) response after once-weekly multiple doses in both children and adults with GHD...
April 18, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29662318/rare-malignant-insulinoma-with-multiple-liver-metastases-derived-from-ectopic-pancreas-3-year-follow-up-and-literature-review
#18
Qing Liu, Jianghui Duan, Yumin Zheng, Jie Luo, Xiaopin Cai, Huangying Tan
Here, we report the diagnosis and treatment of a very rare case of malignant insulinoma derived from ectopic pancreas. A middle-aged woman presented with a 6-year history of recurrent hypoglycemia with multiple lesions in liver. Admission workup revealed elevated serum insulin and C-peptide, as well as multiple lesions in the liver (largest being 4.3 cm), enlarged lymph nodes around the pancreas, and a lesion (of 3.5 cm) at the proximal jejunum, as shown by contrast computed tomography (CT). Liver biopsy showed the lesions to be well-differentiated neuroendocrine tumors, grade G1...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29661273/irs-1-acts-as-an-endocytic-regulator-of-igf-i-receptor-to-facilitate-sustained-igf-signaling
#19
Yosuke Yoneyama, Peter Lanzerstorfer, Hideaki Niwa, Takashi Umehara, Takashi Shibano, Shigeyuki Yokoyama, Kazuhiro Chida, Julian Weghuber, Fumihiko Hakuno, Shin-Ichiro Takahashi
Insulin-like growth factor-I receptor (IGF-IR) preferentially regulates the long-term IGF activities including growth and metabolism. Kinetics of ligand-dependent IGF-IR endocytosis determines how IGF induces such downstream signaling outputs. Here, we find that the insulin receptor substrate (IRS)-1 modulates how long ligand-activated IGF-IR remains at the cell surface before undergoing endocytosis in mammalian cells. IRS-1 interacts with the clathrin adaptor complex AP2. IRS-1, but not an AP2-binding-deficient mutant, delays AP2-mediated IGF-IR endocytosis after the ligand stimulation...
April 11, 2018: ELife
https://www.readbyqxmd.com/read/29656504/efficacy-and-safety-of-myl-1501d-vs-insulin-glargine-in-patients-with-type-1-diabetes-after-52-weeks-results-of-the-instride-1-phase-iii-study
#20
Thomas C Blevins, Abhijit Barve, Bin Sun, Michael Ankersen
AIM: To test the safety and efficacy of MYL-1501D, a proposed insulin glargine biosimilar, in patients with type 1 diabetes mellitus (T1DM). METHODS: The safety and efficacy of MYL-1501D and reference insulin glargine were evaluated in INSTRIDE 1, a 52-week, open-label, randomized, phase III study in patients with T1DM. The primary objective was to determine whether once-daily MYL-1501D was non-inferior to once-daily insulin glargine when administered in combination with mealtime insulin lispro based on change in glycated haemoglobin (HbA1c) from baseline to week 24...
April 15, 2018: Diabetes, Obesity & Metabolism
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