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Long acting insulin

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https://www.readbyqxmd.com/read/29351486/different-physiological-roles-of-insulin-receptors-in-mediating-nutrient-metabolism-in-zebrafish
#1
Bin-Yuan Yang, Gang Zhai, Yu-Long Gong, Jing-Zhi Su, Xu-Yan Peng, Guo-Hui Shang, Dong Han, Jun-Yan Jin, Hao-Kun Liu, Zhen-Yu Du, Zhan Yin, Shou-Qi Xie
Insulin, the most potent anabolic hormone, is critical for somatic growth and metabolism in vertebrates. Type 2 diabetes, which is the primary cause of hyperglycemia, results from an inability of insulin to signal glycolysis and gluconeogenesis. Our previous study showed that double knockout of insulin receptor a (insra) and b (insrb) caused β-cell hyperplasia and lethality from 5 dpf to 16 dpf. In this study, we characterized the physiological roles of Insra and Insrb, in somatic growth and fueling metabolism, respectively...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29341461/effect-of-immediate-and-prolonged-glp-1-receptor-agonist-administration-on-uric-acid-and-its-kidney-clearance-post-hoc-analyses-of-four-clinical-trials
#2
Lennart Tonneijck, Marcel H A Muskiet, Mark M Smits, Petter Bjornstad, Mark H H Kramer, Michaela Diamant, Ewout J Hoorn, Jaap A Joles, Daniël H van Raalte
AIMS: To determine effects of glucagon-like peptide (GLP)-1 receptor agonists (RA) on uric acid (UA)-levels and kidney UA-clearance. MATERIAL AND METHODS: Post-hoc analyses of four controlled clinical trials, which assessed actions of GLP-1RA-administration on kidney physiology. Immediate effects of GLP-1RA exenatide-infusion versus placebo was determined in 9 healthy overweight males (Study-A) and in 52 overweight T2DM-patients (Study-B). Effects were also examined of 12-week long-acting GLP-1RA liraglutide versus placebo in 36 overweight T2DM-patients (Study-C) and of 8-week short-acting GLP-1RA lixisenatide versus once-daily titrated insulin-glulisine in 35 overweight T2DM-patients (Study-D)...
January 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29334997/effects-of-three-frequencies-of-self-monitored-blood-glucose-on-hba1c-and-quality-of-life-in-patients-with-type-2-diabetes-with-once-daily-insulin-and-stable-control-a-randomized-trial
#3
Johanna Hortensius, Nanne Kleefstra, Gijs W D Landman, Bas T Houweling, Klaas H Groenier, Jaap J van der Bijl, Henk Bilo
OBJECTIVE: The optimal frequency of self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes (T2DM) with stable glycemic control is unknown. This study investigated effects of 3 frequencies of SMBG on glycemic control and quality of life after 9 months in patients using one long-acting insulin injection a day. In an open-label, multi-center, primary-care, parallel (1:1:1) randomized trial in the Netherlands including patients with T2DM, HbA1c ≤ 58 mmol/mol (≤ 7...
January 15, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29330446/effect-of-puerarin-in-promoting-fatty-acid-oxidation-by-increasing-mitochondrial-oxidative-capacity-and-biogenesis-in-skeletal-muscle-in-diabetic-rats
#4
Xiu-Fang Chen, Lei Wang, Yong-Zheng Wu, Shi-Yu Song, Hai-Yan Min, Yan Yang, Xuan He, Qiao Liang, Long Yi, Yong Wang, Qian Gao
BACKGROUND: Type 2 diabetes is characterized by dyslipidemia and the accumulation of lipids in non-adipose tissue, including skeletal muscle. Puerarin, which is a natural isoflavonoid isolated from the root of the plant Pueraria lobata, has been shown to have antidiabetic activity. However, the lipid-reducing effect of puerarin, in particular in skeletal muscle, has not yet been addressed. METHODS: We examined the effect of puerarin on mitochondrial function and the oxidation of fatty acids in the skeletal muscle of high-fat diet/streptozotocin-induced diabetic rats...
January 12, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29311640/a-specific-form-of-prefibrillar-aggregates-that-functions-as-a-precursor-of-amyloid-nucleation
#5
Naoki Yamamoto, Shoko Tsuhara, Atsuo Tamura, Eri Chatani
Non-fibrillar protein aggregates that appear in the earlier stages of amyloid fibril formation are sometimes considered to play a key role in amyloid nucleation; however, the structural features of these aggregates currently remain unclear. We herein identified a characteristic pathway of fibril formation by human insulin B chain, in which two major species of prefibrillar aggregates were identified. Based on the time-resolved tracking of this pathway with far-UV circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and 1H-NMR spectroscopy, the first prefibrillar aggregate with a hydrodynamic diameter of approximately 70 nm accumulated concomitantly with the formation of a β-sheet structure, and the size further evolved to 130 nm with an additional structural development...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#6
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29289540/a-randomized-controlled-study-comparing-a-dpp4-inhibitor-linagliptin-and-basal-insulin-glargine-in-patients-with-type-2-diabetes-in-long-term-care-and-skilled-nursing-facilities-linagliptin-ltc-trial
#7
Guillermo E Umpierrez, Saumeth Cardona, David Chachkhiani, Maya Fayfman, Sahebi Saiyed, Heqiong Wang, Priyathama Vellanki, J Sonya Haw, Darin E Olson, Francisco J Pasquel, Theodore M Johnson
OBJECTIVES: Safe and easily implemented treatment regimens are needed for the management of patients with type 2 diabetes mellitus (T2DM) in long-term care (LTC) and skilled nursing facilities. DESIGN: This 6-month open-label randomized controlled trial compared the efficacy and safety of a DPP4 inhibitor (linagliptin) and basal insulin (glargine) in LTC residents with T2DM. SETTINGS: Three LTC institutions affiliated with a community safety-net hospital, US Department of Veterans Affairs and Emory Healthcare System in Atlanta, Georgia...
December 27, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/29276400/challenges-and-unmet-needs-in-basal-insulin-therapy-lessons-from-the-asian-experience
#8
REVIEW
Wing Bun Chan, Jung Fu Chen, Su-Yen Goh, Thi Thanh Huyen Vu, Iris Thiele Isip-Tan, Sony Wibisono Mudjanarko, Shailendra Bajpai, Maria Aileen Mabunay, Pongamorn Bunnag
Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessary to achieve optimal glycemic control. Even so, glycemic control may remain suboptimal in a significant proportion of patients. Unique circumstances in Asia (eg, limited resources, management of diabetes primarily in nonspecialist settings, and patient populations that are predominantly less educated) coupled with the limitations of current basal insulin options (eg, risk of hypoglycemia and dosing time inflexibility) amplify the challenge of optimal basal insulin therapy in Asia...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/29275961/mtorc1-signaling-a-double-edged-sword-in-diabetic-%C3%AE-cells
#9
REVIEW
Amin Ardestani, Blaz Lupse, Yoshiaki Kido, Gil Leibowitz, Kathrin Maedler
The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of metabolic and nutrient cues that integrates environmental inputs into downstream signaling pathways to control cellular metabolism, growth, and survival. While numerous in vitro and in vivo studies reported the positive functions of mTORC1 in the regulation of β cell survival and proliferation under physiological conditions, more recent work demonstrates the opposite in the long term; this is exemplified by the constitutive inappropriate hyper-activation of mTORC1 in diabetic islets or β cells under conditions of increased β cell stress and metabolic demands...
December 20, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29275047/reduced-lordosis-and-enhanced-aggression-in-paced-and-non-paced-mating-in-diabetic-female-rats
#10
Abigail K Hernández-Munive, Daniela Rebolledo-Solleiro, Elisa Ventura-Aquino, Alonso Fernández-Guasti
BACKGROUND: Clinical studies have shown altered sexual function in people with diabetes; basic science studies, using the streptozotocin (STZ)-induced animal model of type 1 diabetes mellitus (DM1), have consistently reported decreased sexual behavior in hyperglycemic female animals, but features of sexual motivation and aggressive behavior have not been explored in these animals. AIM: To study several parameters that denote sexual motivation in STZ-treated female rats and to compare behavioral features of sexual behavior and aggression in non-paced mating (NPM) and paced mating (PM) conditions...
December 20, 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29273485/a-first-in-man-phase-1-trial-for-long-acting-transcon-growth-hormone
#11
David Gilfoyle, Eva Mortensen, Eva Dam Christoffersen, Jonathan A Leff, Michael Beckert
TransCon growth hormone (GH) is a sustained-release inactive prodrug consisting of unmodified GH transiently bound to an inert carrier molecule designed to release fully active GH over a one-week period. This was a first-in-man phase 1 randomized trial was to evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of TransCon GH as compared to equivalent doses of daily GH (Omnitrope) or placebo in healthy adults. Forty-four healthy male adults were randomized to 4 cohorts of 11 subjects, distributed in a 7:2:2 ratio (TransCon GH: Omnitrope: placebo)...
December 5, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/29258401/preventable-adrs-leading-to-hospitalization-results-of-a-long-term-prospective-safety-study-with-6-427-adr-cases-focusing-on-elderly-patients
#12
S Schmiedl, M Rottenkolber, J Szymanski, B Drewelow, W Siegmund, M Hippius, K Farker, I R Guenther, J Hasford, P A Thuermann
BACKGROUND: Studies evaluating the impact of age and potentially inappropriate medication (PIM) on avoidable adverse drug reactions (ADRs) are scarce. METHODS: In this prospective, multi-center, long-term (8.5 years) observational study, we analysed ADRs leading to hospitalization in departments of internal medicine. ADRs causality and preventability were assessed using standardised algorithms. PIM was defined based on the PRISCUS-list. Multivariate analyses and estimation of ADR incidence rates were conducted...
February 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29225702/the-influence-of-dopamine-beta-hydroxylase-and-catechol-o-methyltransferase-gene-polymorphism-on-the-efficacy-of-insulin-detemir-therapy-in-patients-with-type-2-diabetes-mellitus
#13
Tomislav Bozek, Antonela Blazekovic, Matea Nikolac Perkovic, Kristina Gotovac Jercic, Aleksandra Sustar, Lea Smircic-Duvnjak, Tiago F Outeiro, Nela Pivac, Fran Borovecki
Background: Type II diabetes is an important health problem with a complex connection to obesity, leading to a broad range of cardiovascular complications. Insulin therapy often results in weight gain and does not always ensure adequate glycemic control. However, previous studies reported that insulin detemir is an efficient long-acting insulin with a weight sparing effect. The aim of this study was to determine the association of catechol O-methyltransferase (COMT) Val108/158Met and dopamine-beta-hydroxylase (DBH) 1021C/T polymorphisms with the effectiveness of insulin detemir in achieving glucose control and body weight control...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29223807/design-synthesis-and-biological-evaluation-of-deuterated-phenylpropionic-acid-derivatives-as-potent-and-long-acting-free-fatty-acid-receptor-1-agonists
#14
Zheng Li, Chunxia Liu, Xue Xu, Wei Shi, Huilan Li, Yuxuan Dai, Xingguang Cai, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancement of glucose-stimulated insulin secretion. Takeda's compound 1 has robustly in vitro activity for FFA1, but it has been suffered from poor pharmacokinetic (PK) profiles because the phenylpropanoic acid is vulnerable to β-oxidation. To identify orally available agonists, we tried to interdict the metabolically labile group by incorporating two deuterium atoms at the α-position of phenylpropionic acid. Interestingly, the differences of physicochemical properties between hydrogen and deuterium are quite small, but there are many differences in the structure-activity relationship between phenylpropionic acid series and present deuterated series...
December 5, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29197579/microfluidic-production-of-bioactive-fibrin-micro-beads-embedded-in-crosslinked-collagen-used-as-an-injectable-bulking-agent-for-urinary-incontinence-treatment
#15
Vardar E, Larsson Hm, Simone Allazetta, Engelhardt Em, Pinnagoda K, Vythilingam G, Hubbell Ja, Lutolf Mp, Frey P
Endoscopic injection of bulking agents has been widely used to treat urinary incontinence, often due to urethral sphincter complex insufficiency. The aim of the study was to develop a novel injectable bioactive collagen-fibrin bulking agent restoring long-term continence by functional muscle tissue regeneration. Fibrin micro-beads were engineered using a droplet microfluidic system. They had an average diameter of 140 μm, and recombinant fibrin-binding insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1) was covalently conjugated to the beads...
November 29, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29195063/metabolic-and-endocrine-role-of-adipose-tissue-during-lactation
#16
J P McNamara, K Huber
The adipose tissue serves an essential role for survival and reproduction in mammals, especially females. It serves primarily as an energy storage organ and is directly linked to the reproductive success of mammals. In wild animals, adipose tissue function is linked to seasonality of the food supply to support fetal growth and milk production. Adipose tissue depots in ruminants and non-ruminants can secrete many signal molecules (adipokines) that act as hormones and as pro- and anti-inflammatory cytokines. The visceral adipose tissue especially appears to be more endocrinologically active than other adipose depots...
December 1, 2017: Annual Review of Animal Biosciences
https://www.readbyqxmd.com/read/29179857/transition-from-intravenous-insulin-to-subcutaneous-long-acting-insulin-in-critical-care-patients-on-enteral-or-parenteral-nutrition
#17
Analía Ramos, Lluis Zapata, Paula Vera, Antoni J Betbese, Antonio Pérez
BACKGROUND AND AIMS: The optimal initial dose of subcutaneous (SC) insulin after intravenous (IV) infusion is controversial, especially in patients receiving continuous enteral nutrition (EN) or total parenteral nutrition (TPN). The aim of this study was to evaluate the strategy used at our hospital intensive care unit (ICU) in patients switched from IV insulin to SC insulin glargine while receiving EN or TPN. DESIGN AND METHODS: A retrospective analysis was made of 27 patients on EN and 14 on TPN switched from IV infusion insulin to SC insulin...
December 2017: Endocrinología, Diabetes y Nutrición
https://www.readbyqxmd.com/read/29176006/gpr120-mechanism-of-action-role-and-potential-for-medical-applications
#18
Hanna Karakuła-Juchnowicz, Joanna Róg, Dariusz Juchnowicz, Justyna Morylowska-Topolska
G protein-coupled receptors (GPCRs) constitute a family of transmembrane proteins that mediate many cellular processes. GPR120/FFAR4, a receptor from this family that is activated by fatty acids, has received considerable attention recently. This paper presents a literature review concerning the role of GPR120 and its mechanism of action in animal and human studies as well as the potential use of GPR120 for the treatment of chronic diseases. Two electronic databases - Medline and Google Scholar - were searched for available studies addressing the review topic that were written in English and published from 2000 to June 2017...
November 19, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/29175324/lixisenatide-reduces-amyloid-plaques-neurofibrillary-tangles-and-neuroinflammation-in-an-app-ps1-tau-mouse-model-of-alzheimer-s-disease
#19
Hong-Yan Cai, Jun-Ting Yang, Zhao-Jun Wang, Jun Zhang, Wei Yang, Mei-Na Wu, Jin-Shun Qi
Type 2 diabetes mellitus (T2DM) has been identified as a high risk factor for Alzheimer's disease (AD). The impairment of insulin signaling has been found in AD brain. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, normalises insulin signaling and acts as a neuroprotective growth factor. We have previously shown that the long-lasting GLP-1 receptor (GLP-1R) agonist lixisenatide plays an important role in memory formation, synaptic plasticity and cell proliferation of rats. In the follow-up study, we analysed the neuroprotective effect and mechanism of lixisenatide, injected for 60 days at 10 nmol/kg i...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29171021/xenopus-glp-1-derived-and-pegylated-glp-1-receptor-agonists-long-acting-hypoglycemic-and-insulinotropic-activities-with-potential-therapeutic-utilities
#20
Jing Han, Yingying Fei, Feng Zhou, Xinyu Chen, Ying Zhang, Lin Liu, Junjie Fu
BACKGROUND AND PURPOSE: Incretin-based therapies based on glucagon-like peptide-1 (GLP-1) receptor agonists are effective methods for treating type 2 diabetes. Numerous research efforts are focused on the development of long-acting GLP-1 receptor agonists. However, all GLP-1 receptor agonists in clinical use or in clinical development are based on human GLP-1 or Gila GLP-1. We previously identified xGLP-1B as a potent GLP-1 receptor agonist based on Xenopus GLP-1. EXPERIMENTAL APPROACH: To further modify the structure of xGLP-1B, alanine scanning was performed to study the structure-activity relationship of xGLP-1B...
November 24, 2017: British Journal of Pharmacology
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