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https://www.readbyqxmd.com/read/28635658/asperentin-b-a-new-inhibitor-of-the-protein-tyrosine-phosphatase-1b
#1
Jutta Wiese, Hülya Aldemir, Rolf Schmaljohann, Tobias A M Gulder, Johannes F Imhoff
In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillussydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28609372/pancreatic-polypeptide-cell-proliferation-in-the-pancreas-and-duodenum-coexisting-in-a-patient-with-pancreatic-adenocarcinoma-treated-with-a-glp-1-analog
#2
Geoffrey A Talmon, J David Wren, Christophe L Nguyen, Parviz M Pour
A partial pancreaticogastrodudenectomy was performed on a 66-year old man with type 2 diabetes mellitus because of an invasive, moderately differentiated adenocarcinoma in the head of the pancreas. In the adjacent grossly normal tissue of the uncinate process, there was a massive proliferation of pancreatic polypeptide (PP) cells confined to this region and showed invasive pattern. Strikingly, in the heaped area of his duodenum, there was a strikingly large number of PP, glucagon, a few insulin cells in a mini-islet-like patterns composed of glucagon and insulin cells...
July 2017: Pancreas
https://www.readbyqxmd.com/read/28590908/biomimetic-insulin-imprinted-polymer-nanoparticles-as-a-potential-oral-drug-delivery-system
#3
Pijush Kumar Paul, Alongkot Treetong, Roongnapa Suedee
In this study, we investigate molecularly imprinted polymers (MIPs), which form a three-dimensional image of the region at and around the active binding sites of pharmaceutically active insulin or are analogous to b cells bound to insulin. This approach was employed to create a welldefined structure within the nanospace cavities that make up functional monomers by cross-linking. The obtained MIPs exhibited a high adsorption capacity for the target insulin, which showed a significantly higher release of insulin in solution at pH 7...
June 27, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/28577277/in-vitro-production-of-insulin-responsive-skeletal-muscle-tissue-from-mouse-embryonic-stem-cells-by-spermine-induced-differentiation-method
#4
Mikako Saito, Ayano Ishida, Shota Nakagawa
The treatment of an embryoid body with spermine for a short duration can trigger the generation of a 3-dimensional multilayer myotube sheet (MMTS) that shows pulsatile activity. MMTS was previously characterized as a model of skeletal muscle tissue. In the present work, the insulin responsiveness of MMTS was investigated because it is an essential function for a model of skeletal muscle. The glucose uptake activity of MMTS was analyzed by confocal microscopy using fluorescent glucose analogs, namely 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) and its L-glucose counterpart, 2-NBDLG...
June 2, 2017: Human Cell
https://www.readbyqxmd.com/read/28555111/novel-glp-1-analog-supaglutide-reduces-hfd-induced-obesity-associated-with-increased-ucp-1-in-white-adipose-tissue-in-mice
#5
Yun Wan, Xi Bao, Jiabao Huang, Xiangyu Zhang, Wenjuan Liu, Qiaoli Cui, Dongdong Jiang, Zhihong Wang, Rui Liu, Qinghua Wang
GLP-1, an important incretin hormone plays an important role in the regulation of glucose homeostasis. However, the therapeutic use of native GLP-1 is limited due to its short half-life. We recently developed a novel GLP-1 mimetics (supaglutide) by genetically engineering recombinant fusion protein production techniques. We demonstrated that this formulation possessed long-lasting GLP-1 actions and was effective in glycemic control in both type 1 and type 2 diabetes rodent models. Here, we investigated the effects of supaglutide in regulating energy homeostasis in obese mice...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28553603/an-audit-of-insulin-usage-and-insulin-injection-practices-in-a-large-indian-cohort
#6
Manash P Baruah, Sanjay Kalra, Saptarshi Bose, Jumi Deka
INTRODUCTION: Insulin remains the cornerstone of therapy in a substantial number of patients with type 2 diabetes mellitus (T2DM). Inadequate knowledge regarding insulin usage is likely to influence its acceptance and adherence, and outcome of therapy, underscoring great need to investigate knowledge, attitude, and practice of insulin usage in patients with T2DM. METHODOLOGY: A cross-sectional registry-based retrospective study analyzed data collected from 748 respondents (male: 466, female: 282), mostly from high or middle economic status, who were enrolled as outpatient in a referral clinic during last 10 years (2006-2016), to assess the general characteristics of patients with type 2 diabetes and their baseline knowledge, attitude, and practice of insulin usage and injection practices...
May 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28537449/understanding-how-pharmacokinetic-and-pharmacodynamic-differences-of-basal-analog-insulins-influence-clinical-practice
#7
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
#8
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 adipocyte differentiation of 3T3-L1 cells but resulted in a moderate (18-19%) reduction of stored TGs...
May 18, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#9
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
#10
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)...
July 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28509691/development-of-glucose-responsive-smart-insulin-systems
#11
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
#12
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
#13
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: The authors searched the PubMed database to review TR and the action of thyromimetics in vitro and in animal models...
June 9, 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
#14
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
#15
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
#16
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
#17
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
#18
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...
July 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
#19
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
#20
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...
June 6, 2017: Analytical Chemistry
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