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https://www.readbyqxmd.com/read/28336368/novel-strategies-in-the-oral-delivery-of-antidiabetic-peptide-drugs-insulin-glp-1-and-its-analogs
#1
REVIEW
Ruba Ismail, Ildikó Csóka
As diabetes is a complex disorder being a major cause of mortality and morbidity in epidemic rates, continuous research has been done on new drug types and administration routes. Up to now, a large number of therapeutic peptides have been produced to treat diabetes including insulin, glucagon-like peptide-1 (GLP-1) and its analogs. The most common route of administration of these antidiabetic peptides is parenteral. Due to several drawbacks associated with this invasive route, delivery of these antidiabetic peptides by the oral route has been a goal of pharmaceutical technology for many decades...
March 21, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28331865/growth-hormone-utilization-review-in-a-pediatric-primary-care-setting
#2
Fatemeh Sayarifard, Fereshteh Bakhshi Imcheh, Shirinsadat Badri, Toktam Faghihi, Mostafa Qorbani, Mania Radfar
OBJECTIVE: One of the main problems facing public health providers and administrators in many countries is ensuring the rational use of high-cost drugs. In this regard, on-going process of medication use evaluation can be considered as a useful tool. In this study, we evaluated certain usage aspects of a highly-cost medication, that is, recombinant growth hormone (GH). METHODS: This cross-sectional study conducted from August 2012 to August 2014. Children receiving GH ± gonadotropin releasing hormone (GnRH) analogs were included in the study...
January 2017: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/28325730/glucose-oxidation-positively-regulates-glucose-uptake-and-improves-cardiac-function-recovery-after-myocardial-reperfusion
#3
Tingting Li, Jie Xu, Xinghua Qin, Zuoxu Hou, Yongzheng Guo, Zhenhua Liu, Jianjiang Wu, Hong Zheng, Xing Zhang, Feng Gao
Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia/reperfusion injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. Here we found that glucose uptake was remarkably diminished in myocardium following reperfusion in Sprague-Dawley rats as detected by 18F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by 3 folds and GLUT4 translocation remained unchanged compared with those of sham rats...
March 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324110/effects-of-metreleptin-in-pediatric-patients-with-lipodystrophy
#4
Rebecca J Brown, Cristina Adelia Meehan, Elaine Cochran, Kristina I Rother, David E Kleiner, Mary Walter, Phillip Gorden
Context: Lipodystrophy syndromes are rare disorders of deficient adipose tissue. Metreleptin, a human analog of leptin, improved metabolic abnormalities in mixed cohorts of leptin-deficient children and adults with lipodystrophy. Objective: Determine effects of metreleptin on diabetes, hyperlipidemia, non-alcoholic fatty liver disease (NAFLD), growth, and puberty in leptin-deficient pediatric patients with lipodystrophy. Design: Prospective, single-arm, open-label studies with continuous enrollment since 2000...
January 23, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324014/variation-in-the-insulin-like-growth-factor-1-gene-in-primates
#5
Peter Rotwein
Insulin-like growth factor 1 (IGF1) is a multifunctional peptide that is involved in a wide range of physiological and patho-physiological processes in many animal species, ranging from somatic growth in children to metabolism, and tissue regeneration and repair in adults. The IGF1 gene is under multifactorial regulation in the few species in which it has been studied, with major control being exerted by growth hormone (GH) through a gene expression pathway involving inducible binding of the STAT5b transcription factor to dispersed enhancer elements...
January 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28319665/synthesis-of-four-disulfide-insulin-analogs-via-sequential-disulfide-bond-formation
#6
Fangzhou Wu, John P Mayer, Vasily G Gelfanov, Fa Liu, Richard D DiMarchi
Naturally-occurring, multiple cysteine-containing peptides are a structurally unique class of compounds with a wide range of therapeutic and diagnostic applications. The development of reliable, and precise chemical methods for their preparation is of paramount importance to facilitate exploration of their utility. We report an efficient approach based on stepwise, sequentially directed disulfide bond formation, exemplified here by the synthesis of four-disulfide bond containing insulin analogs. The cysteine protections consisted of tert-butylthiol (StBu), thiol-trimethoxyphenyl (STmp), trityl (Trt), 4-methoxytrityl (Mmt), S-acetamidomethyl (Acm) and tert-butyl (tBu)...
March 20, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28317899/minocycline-treatment-suppresses-juvenile-development-and-growth-by-attenuating-insulin-tor-signaling-in-drosophila-animal-model
#7
Hyun Myoung Yun, Sujin Noh, Seogang Hyun
Minocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296883/soluble-insulin-analogs-combining-rapid-and-long-acting-hypoglycemic-properties-from-an-efficient-e-coli-expression-system-to-a-pharmaceutical-formulation
#8
Diana Mikiewicz, Anna Bierczyńska-Krzysik, Agnieszka Sobolewska, Dorota Stadnik, Monika Bogiel, Monika Pawłowska, Anna Wójtowicz-Krawiec, Piotr A Baran, Natalia Łukasiewicz, Agnieszka Romanik-Chruścielewska, Iwona Sokołowska, Jacek Stadnik, Piotr Borowicz, Grażyna Płucienniczak, Andrzej Płucienniczak
The discovery of insulin led to a revolution in diabetes management. Since then, many improvements have been introduced to insulin preparations. The availability of molecular genetic techniques has enabled the creation of insulin analogs by changing the structure of the native protein in order to improve the therapeutic properties. A new expression vector pIBAINS for production of four recombinant human insulin (INS) analogs (GKR, GEKR, AKR, SR) was constructed and overexpressed in the new E. coli 20 strain as a fusion protein with modified human superoxide dismutase (SOD)...
2017: PloS One
https://www.readbyqxmd.com/read/28291683/a-pegylated-analog-of-short-length-neuromedin-u-with-potent-anorectic-and-anti-obesity-effects
#9
Hiroshi Inooka, Kotaro Sakamoto, Tokuyuki Shinohara, Yasushi Masuda, Michiko Terada, Satoshi Kumano, Kotaro Yokoyama, Jiro Noguchi, Naoki Nishizawa, Hidenori Kamiguchi, Hisashi Fujita, Taiji Asami, Shiro Takekawa, Tetsuya Ohtaki
Neuromedin U (NMU) is a neuropeptide known to regulate food intake and energy homeostasis that is widely distributed in the gastrointestinal tract, hypothalamus, and pituitary. A short form of NMU, porcine NMU-8 has potent agonist activity for the receptors NMUR1 and NMUR2; however, its short half-life precludes its effective use in vivo. To address this limitation, we designed and synthesized NMU-8 analogs modified by polyethylene glycol (PEG) with a molecular weight of 30kDa (PEG30k) via a variety of linkers (i...
February 21, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28287854/polypharmacy-and-adherence-to-adjuvant-endocrine-therapy-for-breast-cancer
#10
Gregory S Calip, Shan Xing, Da-Hae Jun, Wan-Ju Lee, Kent F Hoskins, Naomi Y Ko
PURPOSE: Many patients with breast cancer are treated for other conditions and experience polypharmacy with multiple concurrent medications. Our aim was to evaluate polypharmacy in relation to adherence to adjuvant endocrine therapy (AET) in breast cancer. METHODS: We conducted a retrospective cohort study of women with incident, invasive breast cancer initiating AET (tamoxifen, letrozole, anastrozole, exemestane) between 2009 and 2013 in the Truven Health MarketScan Database...
March 13, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28277867/the-role-of-the-new-basal-insulin-analogs-in-addressing-unmet-clinical-needs-in-people-with-type-1-and-type-2-diabetes
#11
Rosemarie Lajara, Eda Cengiz, Robert J Tanenberg
BACKGROUND: Despite improvements in anti-hyperglycemic therapies, there are many unmet clinical needs that hinder successful glycemic control in people being treated with current basal insulin analogs. OBJECTIVE: This paper reviews the unmet needs associated with current basal insulin therapy and describes the most recent basal insulins for the treatment of diabetes. METHODS: PubMed was searched for articles on basal insulin analogs published between 2000 and April 2016...
March 24, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28274181/structure-of-the-carboxypeptidase-b-complex-with-n-sulfamoyl-l-phenylalanine-a-transition-state-analog-of-non-specific-substrate
#12
Valery Akparov, Vladimir Timofeev, Ilyas Khaliullin, Vytas Švedas, Inna Kuranova
Carboxypeptidase B (EC 3.4.17.2) (CPB) is commonly used in the industrial insulin production and as a template for drug design. However its ability to discriminate substrates with hydrophobic, hydrophilic and charged side chains is not well understood. We report structure of CPB complex with a transition-state analogue N-sulfamoyl-L-phenylalanine solved at 1.74Å. The study provided an insight into structural basis of CPB substrate specificity. Ligand binding is affected by structure-depended conformational changes of Asp255 in S1'-subsite, interactions with Asn144 and Arg145 in C-terminal binding subsite, and Glu270 in the catalytic center...
March 8, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28270441/insulin-sensitizer-prevents-and-ameliorates-experimental-type-1-diabetes
#13
Michael Valitsky, Amnon Hoffman, Terry Unterman, Jacob Bar-Tana
Insulin-dependent type-1 diabetes (T1D) is driven by autoimmune beta-cell failure, whereas systemic resistance to insulin is considered the hallmark of insulin-independent type-2 diabetes (T2D). In contrast to this canonical dichotomy, insulin resistance appears to precede the overt diabetic stage of T1D and to predict its progression, implying that insulin sensitizers may change the course of T1D. However, previous attempts to ameliorate T1D in animal models or patients by insulin sensitizers have largely failed...
March 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28260207/biochemical-assessment-of-disease-control-in-acromegaly-reappraisal-of-the-glucose-suppression-test-in-somatostatin-analogue-sa-treated-patients
#14
Mai Christiansen Arlien-Søborg, Christian Trolle, Elin Alvarson, Amanda Bæk, Jakob Dal, Jens Otto Lunde Jørgensen
BACKGROUND: It is recommended not to measure growth hormone during oral glucose suppression (oral glucose tolerance test) during somatostatin analog treatment in acromegaly. However, we have observed that failure to suppress growth hormone in response to oral glucose tolerance test during somatostatin analog unmasks insufficient disease control and hypothesize that somatostatin analog also induces insufficient growth hormone suppression to mixed meals. METHODS: We therefore compared serum growth hormone levels during two mixed meals in patients with controlled insulin-like growth factor-I levels after either surgery alone (n = 9) or somatostatin analog treatment (n = 9)...
March 4, 2017: Endocrine
https://www.readbyqxmd.com/read/28257286/regional-differences-in-insulin-therapy-regimens-in-five-european-countries%C3%A2
#15
Wolfgang Rathmann, Marcin Czech, Edward Franek, Karel Kostev
AIMS: The purpose of this study was to investigate differences of insulin therapy regimens in five European countries. METHODS: Proportions of basal bolus therapy (intensified insulin therapy (ICT), basal insulin supported oral therapy (BOT), conventional therapy (CT), and short-acting prandial insulin (SIT) among insulin-treated diabetes patients in Germany (n = 64,055), the UK (n = 6,740), and France (n = 4,779) were estimated using representative general medicine practice databases (Disease Analyzer: 2014)...
March 3, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28243067/insulin-adherence-and-persistence-among-chinese-patients-with-type-2-diabetes-a-retrospective-database-analysis
#16
Xiaoning He, Liming Chen, Ke Wang, Haiya Wu, Jing Wu
OBJECTIVE: To assess adherence and persistence to insulin therapy and identify its associated factors among Chinese insulin-naïve patients with type 2 diabetes (T2D). METHODS: Tianjin Urban Employee Basic Medical Insurance claims database was used (2008-2011). Adult patients with T2D who initiated insulin therapy during January 2009 through December 2010 and were continuously enrolled for 12 months pre-(baseline) and 12 months post-initiation (follow-up) were included...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28230457/comparative-effectiveness-of-rapid-acting-insulins-in-adults-with-diabetes
#17
Patrick N Racsa, Yunus Meah, Jeffrey J Ellis, Kimberly R Saverno
BACKGROUND: Although there are a variety of insulin products and new delivery modalities available, the absence of direct clinical and economic comparisons can make treatment planning and formulary decision making difficult. Direct comparisons between insulin aspart and insulin lispro from a large heterogeneous population are not available. OBJECTIVE: To assess differences in clinical outcomes, medication adherence, utilization, and total health care costs between aspart and lispro and vial versus pen modalities for administering these short-acting insulin analogs...
March 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28182770/biochemical-and-biophysical-investigations-of-the-interaction-between-human-glucokinase-and-pro-apoptotic-bad
#18
Alix Rexford, Diego A R Zorio, Brian G Miller
The glycolytic enzyme glucokinase (GCK) and the pro-apoptotic protein BAD reportedly reside within a five-membered complex that localizes to the mitochondria of mammalian hepatocytes and pancreatic β-cells. Photochemical crosslinking studies using a synthetic analog of BAD's BH3 domain and in vitro transcription/translation experiments support a direct interaction between BAD and GCK. To investigate the biochemical and biophysical consequences of the BAD:GCK interaction, we developed a method for the production of recombinant human BAD...
2017: PloS One
https://www.readbyqxmd.com/read/28176959/a-systematic-literature-review-on-the-efficacy-effectiveness-gap-comparison-of-randomized-controlled-trials-and-observational-studies-of-glucose-lowering-drugs
#19
REVIEW
Mikkel Z Ankarfeldt, Erpur Adalsteinsson, Rolf Hh Groenwold, M Sanni Ali, Olaf H Klungel
AIM: To identify a potential efficacy-effectiveness gap and possible explanations (drivers of effectiveness) for differences between results of randomized controlled trials (RCTs) and observational studies investigating glucose-lowering drugs. METHODS: A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1) with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i) with sulfonylurea, all with change in glycated hemoglobin (HbA1c) as outcome...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28176886/assessment-of-channeling-bias-among-initiators-of-glucose-lowering-drugs-a-uk-cohort-study
#20
Mikkel Z Ankarfeldt, Brian L Thorsted, Rolf Hh Groenwold, Erpur Adalsteinsson, M Sanni Ali, Olaf H Klungel
BACKGROUND: Channeling bias may occur when a newly marketed drug and an established drug, despite similar indications, are prescribed to patients with different prognostic characteristics (ie, confounding). AIM: To investigate channeling bias and its impact on relative effectiveness of glucagon-like peptide-1 (GLP-1) analogs versus basal insulin and dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylurea. METHODS: In the UK Clinical Practice Research Datalink, patients with type 2 diabetes initiating treatment between 2006 and 2015 were included...
2017: Clinical Epidemiology
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