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https://www.readbyqxmd.com/read/28537449/understanding-how-pharmacokinetic-and-pharmacodynamic-differences-of-basal-analog-insulins-influence-clinical-practice
#1
Jennifer Goldman, Christoph Kapitza, Jeremy Pettus, Tim Heise
This article reviews pharmacokinetic (PK) and pharmacodynamic (PD) concepts relating to the pharmacology of basal insulin analogs. Understanding the pharmacology of currently available long-acting basal insulins and the techniques used to assess PK and PD parameters (e.g. the euglycemic clamp method) is important when considering the efficacy and safety of these agents, and can help in understanding the rationale for specific dosing strategies when tailoring therapy for a specific patient. Basal insulins such as insulin glargine 100 units (U)/mL and insulin detemir show improved PK/PD characteristics compared with the intermediate-acting NPH insulin, with a longer duration of action, a more consistent glucose-lowering effect and less prominent concentration peaks...
May 24, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28528274/angiopoietin-like-8-angptl8-controls-adipocyte-lipolysis-and-phospholipid-composition
#2
Raghavendra Mysore, Gerhard Liebisch, You Zhou, Vesa M Olkkonen, P A Nidhina Haridas
Angiopoietin-like 8 (Angptl8) inhibits lipolysis in the circulation together with Angplt3 and controls post-prandial fat storage in white adipose tissue (WAT). It is strongly induced by insulin in vivo in WAT and in vitro in adipocytes. In this study we addressed the function of Angptl8 in adipocytes by its stable lentivirus-mediated knock-down in 3T3-L1 cells, followed by analyses of triglyceride (TG) storage, lipid droplet (LD) morphology, the cellular lipidome, lipolysis, and gene expression. Depletion of Angptl8 did not drastically affect the adipocytic differentiation of 3T3-L1 cells but resulted in a moderate (18-19%) reduction of stored TGs...
May 17, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#3
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28511140/different-impacts-of-acylated-and-non-acylated-long-acting-insulin-analogs-on-neural-functions-in-vitro-and-in-vivo
#4
Hiroshi Tsuneki, Hitomi Yoshida, Kosuke Endo, Norihiko Mori, Shuji Hosoh, Masaaki Tsuda, Tsutomu Wada, Toshiyasu Sasaoka
AIMS: Centrally administered insulin improves cognitive functions in patients with Alzheimer's disease; however, it remains unknown whether long-acting insulin analogs exert more pronounced effects than insulin. In the present study, we directly compared the effects of insulin and its analogs on neural functions in vitro and in vivo. METHODS: Cultured rat cerebral cortical neurons were treated with insulin, insulin glargine U100 (Gla), insulin detemir (Det), or insulin degludec (Deg)...
May 4, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28509691/development-of-glucose-responsive-smart-insulin-systems
#5
Nischay K Rege, Nelson F B Phillips, Michael A Weiss
PURPOSE OF REVIEW: The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider...
May 15, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28503791/blood-glucose-and-insulin-concentrations-after-octreotide-administration-in-horses-with-insulin-dysregulation
#6
N Frank, P Hermida, A Sanchez-Londoño, R Singh, C M Gradil, C K Uricchio
BACKGROUND: Octreotide is a somatostatin analog that suppresses insulin secretion. HYPOTHESIS: We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. ANIMALS: Twelve horses, N = 5, ID = 7. METHODS: Prospective study. An oral sugar test was performed to assign horses to N and ID groups...
May 15, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28498022/thyroid-hormone-analogs-for-the-treatment-of-dyslipidemia-past-present-and-future
#7
Alessandro P Delitala, Giuseppe Delitala, Paolo Sioni, Giuseppe Fanciulli
OBJECTIVE: Treatment of dyslipidemia is a major burden for public health. Thyroid hormone regulates lipid metabolism by binding the thyroid hormone receptor (TR), but the use of thyroid hormone to treat dyslipidemia is not indicated due to its deleterious effects on heart, bone, and muscle. Thyroid hormone analogs have been conceived to selectively activate TR in the liver, thus reducing potential side effects. METHODS: We searched the PubMed database to review TR and the action of thyromimetics in vitro and in animal models...
May 12, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28490635/the-foxo-transcription-factor-controls-insect-growth-and-development-by-regulating-juvenile-hormone-degradation-in-the-silkworm-bombyx-mori
#8
Baosheng Zeng, Yuping Huang, Jun Xu, Takahiro Shiotsuki, Hua Bai, Subba Reddy Palli, Yongping Huang, Anjiang Tan
Forkhead box O (FOXO) functions as the terminal transcription factor of the insulin signaling pathway and regulates multiple physiological processes in many organisms, including lifespan in insects. However, how FOXO interacts with hormone signaling to modulate insect growth and development is largely unknown. Here, using the transgene-based CRISPR/Cas9 system, we generated and characterized mutants of the silkworm Bombyx mori FOXO (BmFOXO) to elucidate its physiological functions during development of this lepidopteran insect...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28485590/structure-activity-relationship-of-2-4-dichloro-n-3-5-dichloro-4-quinolin-3-yloxy-phenyl-benzenesulfonamide-int131-analogs-for-ppar%C3%AE-targeted-antidiabetics
#9
Rebecca L Frkic, Yuanjun He, Beatriz B Rodriguez, Mi Ra Chang, Dana Kuruvilla, Anthony Ciesla, Andrew D Abell, Theodore M Kamenecka, Patrick R Griffin, John B Bruning
Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor central to fatty acid and glucose homeostasis. PPARγ is the molecular target for type 2 diabetes mellitus (T2DM) therapeutics TZDs (thiazolidinediones), full agonists of PPARγ with robust antidiabetic properties, which are confounded with significant side effects. Partial agonists of PPARγ, such as INT131 (1), have displayed similar insulin-sensitizing efficacy as TZDs, but lack many side effects. To probe the structure-activity relationship (SAR) of the scaffold 1, we synthesized 14 analogs of compound 1 which revealed compounds with higher transcriptional potency for PPARγ and identification of moieties of the scaffold 1 key to high transcriptional potency...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28485429/potato-protease-inhibitor-ii-suppresses-postprandial-appetite-in-healthy-women-a-randomized-double-blind-placebo-controlled-trial
#10
Yong Zhu, Joanne A Lasrado, Jiang Hu
The effect of potato protease inhibitor II (PI2) on postprandial appetite was examined in a randomized double-blind placebo-controlled cross-over trial involving 44 healthy women. In separate test sessions, participants consumed a capsule containing placebo or potato extract standardized to 15 or 30 mg PI2 after overnight fasting. One hour later, a standard 390 kcal breakfast was served. At regular time points during the three-hour period after breakfast, appetite was measured by visual analog scales, and blood samples were collected for assay of cholecystokinin, insulin, and glucose...
May 24, 2017: Food & Function
https://www.readbyqxmd.com/read/28483790/effect-of-hormone-secretory-syndromes-on-neuroendocrine-tumor-prognosis
#11
Wouter T Zandee, Kimberly Kamp, R C S van Adrichem, R A Feelders, Wouter W de Herder
The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete a wider variety of hormones, like insulin, glucagon and gastrin leading to distinct clinical syndromes. Historically mortality in patients with functioning NETs was high due to the complications caused by the hypersecretion of hormones...
May 8, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28482296/is-mercury-exposure-causing-diabetes-metabolic-syndrome-and-insulin-resistance-a-systematic-review-of-the-literature
#12
REVIEW
Cynthia Roy, Pierre-Yves Tremblay, Pierre Ayotte
INTRODUCTION: Several populations are exposed to mercury (Hg) via their environment, occupation or diet. It is hypothesized that Hg exposure can lead to the development of diabetes mellitus (DM). Metabolic syndrome (MS) is also a possible outcome as its symptoms are closely linked to those of DM. METHOD: We conducted a systematic review of the literature by screening Web of Science, MEDLINE, SciFinder and Embase and we included original studies pertaining to the relationship of total Hg exposure (elemental, inorganic or organic) to DM, MS or insulin resistance...
May 5, 2017: Environmental Research
https://www.readbyqxmd.com/read/28482050/parallel-assessment-of-the-effects-of-bisphenol-a-and-several-of-its-analogs-on-the-adult-human-testis
#13
C Desdoits-Lethimonier, L Lesné, P Gaudriault, D Zalko, J P Antignac, Y Deceuninck, C Platel, N Dejucq-Rainsford, S Mazaud-Guittot, B Jégou
STUDY QUESTION: Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? SUMMARY ANSWER: The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. WHAT IS KNOWN ALREADY: The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption...
May 8, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28467848/automated-microfluidic-droplet-based-sample-chopper-for-detection-of-small-fluorescence-differences-using-lock-in-analysis
#14
Jean T Negou, L Adriana Avila, Xiangpeng Li, Tesfagebriel M Hagos, Christopher J Easley
Fluorescence is widely used for small-volume analysis and is a primary tool for on-chip detection in microfluidic devices, yet additional expertise, more elaborate optics, and phase-locked detectors are needed for ultrasensitive measurements. Recently, we designed a microfluidic analog to an optical beam chopper (μChopper) that alternated formation of picoliter volume sample and reference droplets. Without complex optics, the device negated large signal drifts (1/f noise), allowing absorbance detection in a mere 27 μm optical path...
May 11, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28466661/dose-unit-establishment-for-a-new-basal-insulin-using-joint-modeling-of-insulin-dose-and-glycemic-response
#15
Yongming Qu, Junxiang Luo, Parag Garhyan, Caryl J Antalis, Annette M Chang, Scott J Jacober
BACKGROUND: For new insulin analogs with properties that vary from human insulin, defining activity in units of human insulin based on glycemic lowering efficacy may be challenging. Here we present a new method that can be used to quantify a unit dose of an experimental insulin when the traditional euglycemic clamp method is not adequate. METHODS: Joint modeling of insulin dose and the glycemic outcome variable hemoglobin A1c (HbA1c), where both were response variables, was used to evaluate insulin unit potency for basal insulin peglispro (BIL)...
May 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28461341/pglp-1-a-novel-long-acting-dual-function-glp-1-analog-ameliorates-streptozotocin-induced-hyperglycemia-and-inhibits-body-weight-loss
#16
Huashan Gao, Qian Zhao, Ziwei Song, Zhaocong Yang, You Wu, Shanshan Tang, Murad Alahdal, Yanfeng Zhang, Liang Jin
It is well known that glucagon-like peptide 1 (GLP-1) has antidiabetic action. It has 2 distinct functions, an insulinotropic effect dependent on GLP-1 receptor (GLP-1R) and an insulinomimetic effect independent of GLP-1R. However, use of GLP-1 in vivo is limited by its short half-life. Therefore, our lab designed PGLP-1, a novel 2-function candidate peptide as a potential substitute. Using a streptozotocin-induced hyperglycemic mouse model, we demonstrated in vitro and in vivo that PGLP-1 had insulinotropic actions dependent on GLP-1R and insulinomimetic functions independent of GLP-1R...
May 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28449155/mitochondrial-dysfunction-in-diabetic-cardiomyopathy-effect-of-mesenchymal-stem-cell-with-ppar-%C3%AE-agonist-or-exendin-4
#17
Mohamed Abd Elaziz Wassef, Ola M Tork, Laila A Rashed, Walaa Ibrahim, Heba Morsi, Dina Mohamed Mekawy Rabie
Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4...
April 27, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28424924/effects-of-gw002-a-novel-recombinant-human-glucagon-like-peptide-1-glp-1-analog-fusion-protein-on-cho-recombinant-cells-and-bks-db-mice
#18
Wan-Wan Ji, Dong-An Yu, Min Fan, Meng You, You Lu, Er-Bing Li, Ning Xie, Shou-Sheng Yan
AIMS: GLP-1-based strategies have many advantages in treatment of type 2 diabetes mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which limits its clinical application. The purpose of this study was to evaluate the effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by linking the human GLP-1 analog C-terminus to the N-terminus of human serum albumin via a linker, in vitro and in BKS-db mice. METHODS: To determine whether GW002 can activate the GLP-1 receptor in cells, the level of luciferase expression was evaluated in vitro...
April 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28421968/chronic-toxicology-studies-of-basal-insulin-peglispro-in-rats-and-dogs-a-novel-pegylated-insulin-lispro-analog-with-a-prolonged-duration-of-action
#19
Richard A Byrd, Jamie L Blackbourne, Mary Pat Knadler, Albert E Schultze, John L Vahle
Basal insulin peglispro (BIL) consists of insulin lispro with a 20-kDa polyethylene glycol (PEG) moiety covalently attached to lysine B28. Because chronic parenteral administration of PEGylated proteins to animals has sometimes resulted in PEG vacuolation of tissue macrophages, renal tubular cells, and choroid plexus ependymal cells, we investigated whether chronic subcutaneous (sc) injection of BIL in rats (52 weeks) and dogs (39 weeks) was associated with systemic toxicities or other changes, including vacuolation of tissue macrophages, renal tubular cells, and ependymal cells...
April 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28413872/favorable-effect-on-blood-volume-control-in-hemodialysis-patients-with-type-2-diabetes-after-switching-from-insulin-therapy-to-liraglutide-a-human-glucagon-like-peptide-1-analog-results-from-a-pilot-study-in-japan
#20
Masumi Kondo, Masao Toyoda, Moritsugu Kimura, Naoto Ishida, Masafumi Fukagawa
OBJECTIVE: Hemodialysis patients are advised to limit the intake of foods in order to control volume status and body weight (BW). We report the clinical course of five Japanese hemodialysis patients with type 2 diabetes mellitus (T2DM) who were switched from insulin to liraglutide, and the efficacy of the treatment, especially in terms of changes in interdialysis weight gain (IDWG). METHODS: This retrospective pilot study included 5 Japanese hemodialysis patients with T2DM...
April 20, 2017: Tokai Journal of Experimental and Clinical Medicine
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