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insulin and GLP-1 analog

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https://www.readbyqxmd.com/read/27888738/oxyntomodulin-analog-and-exendin-4-derivative-lower-plasma-glucose-in-cattle
#1
S ThanThan, Y Asada, T Saito, K Ochiiwa, H Zhao, S W Naing, H Kuwayama
The present study was undertaken with the aim of examining whether and how exendin-4 (1-3) fragment, ie, Ex-4 (1-3) fragment, contributes to the regulation of glucose. An analog of oxyntomodulin (OXM) ([Gly(2), Glu(3)]-OXM), a glucagon analog ([Gly(2), Glu(3)]-glucagon), and two derivatives of Ex-4 (glucandin and [Gly(2), Glu(3)]-glucandin) were synthesized by substituting with Gly(2), Glu(3) at the N-terminuses of OXM and glucagon and/or by attaching Ex-4 (30-39) amide at the C-terminus of glucagon. Effects of these peptides on plasma insulin and glucose concentrations were investigated in cattle by conducting 3 in vivo experiments...
November 2, 2016: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/27879196/treatment-persistence-in-the-use-of-basal-insulins-in-poland-and-germany%C3%A2
#2
Wolfgang Rathmann, Marcin Czech, Edward Franek, Karel Kostev
AIMS: To compare short-term basal insulin therapy persistence and its predictors in Poland and Germany. METHODS: Persistence was defined as proportions of patients remaining on the initial basal insulin (analogs: Poland: n = 6,889, Germany: n = 454,067; neutral protamine Hagedorn (NPH) insulins: Poland: n = 50,761, Germany: n = 226,064) over 2 years based on nationwide prescription databases (LRx; IMS Health) in Poland and Germany from 2013 to 2015. Persistence was evaluated by Kaplan-Meier curves (log-rank tests)...
November 23, 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27776453/individualized-patient-centred-use-of-lixisenatide-for-the-treatment-of-type-2-diabetes-mellitus
#3
Markolf Hanefeld, Denis Raccah, Louis Monnier
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with hyperglycemia, which can lead to serious vascular complications. Current treatment guidelines place particular emphasis on personalization of therapy. Within this guidance, the use of various second-line therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is recommended under certain circumstances. Areas covered: Factors influencing glucose homeostasis, including gastric emptying and the associated cardiovascular (CV) risk when homeostasis is not maintained, are reviewed...
October 25, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27562982/new-approaches-to-feline-diabetes-mellitus-glucagon-like-peptide-1-analogs
#4
REVIEW
Chen Gilor, Adam J Rudinsky, Melanie J Hall
CLINICAL RELEVANCE: Incretin-based therapies are revolutionizing the field of human diabetes mellitus (DM) by replacing insulin therapy with safer and more convenient long-acting drugs. MECHANISM OF ACTION: Incretin hormones (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) are secreted from the intestinal tract in response to the presence of food in the intestinal lumen. GLP-1 delays gastric emptying and increases satiety. In the pancreas, GLP-1 augments insulin secretion and suppresses glucagon secretion during hyperglycemia in a glucose-dependent manner...
September 2016: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/27436611/liraglutide-prevents-microvascular-insulin-resistance-and-preserves-muscle-capillary-density-in-high-fat-diet-fed-rats
#5
Weidong Chai, Zhuo Fu, Kevin W Aylor, Eugene J Barrett, Zhenqi Liu
Muscle microvasculature critically regulates endothelial exchange surface area to facilitate transendothelial delivery of insulin, nutrients, and oxygen to myocytes. Insulin resistance blunts insulin-mediated microvascular recruitment and decreases muscle capillary density; both contribute to lower microvascular blood volume. Glucagon-like peptide 1 (GLP-1) and its analogs are able to dilate blood vessels and stimulate endothelial cell proliferation. In this study, we aim to determine the effects of sustained stimulation of the GLP-1 receptors on insulin-mediated capillary recruitment and metabolic insulin responses, small arterial endothelial function, and muscle capillary density...
September 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27358756/safety-concerns-over-the-use-of-intestinal-permeation-enhancers-a-mini-review
#6
REVIEW
Fiona McCartney, John P Gleeson, David J Brayden
Intestinal permeation enhancers (PEs) are key components in ∼12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression...
April 2016: Tissue Barriers
https://www.readbyqxmd.com/read/27313194/mechanisms-of-surgical-control-of-type-2-diabetes-glp-1-is-key-factor
#7
REVIEW
Jens Juul Holst, Sten Madsbad
GLP-1 secretion in response to meals is dramatically increased after gastric bypass operations. GLP-1 is a powerful insulinotropic and anorectic hormone, and analogs of GLP-1 are widely used for the treatment of diabetes and recently approved also for obesity treatment. It is, therefore, reasonable to assume that the exaggerated GLP-1 secretion contributes to the antidiabetic and anorectic effects of gastric bypass. Indeed, human experiments with the GLP-1 receptor antagonist, Exendin 9-39, have shown that the improved insulin secretion, which is responsible for part of the antidiabetic effect of the operation, is reduced and or abolished after GLP-1 receptor blockade...
July 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/27297962/oral-2-oleyl-glyceryl-ether-improves-glucose-tolerance-in-mice-through-the-gpr119-receptor
#8
H A Hassing, M S Engelstoft, R M Sichlau, A N Madsen, J F Rehfeld, J Pedersen, R M Jones, J J Holst, T W Schwartz, M M Rosenkilde, H S Hansen
The intestinal G protein-coupled receptor GPR119 is a novel metabolic target involving glucagon-like peptide-1 (GLP-1)-derived insulin-regulated glucose homeostasis. Endogenous and diet-derived lipids, including N-acylethanolamines and 2-monoacylglycerols (2-MAG) activate GPR119. The purpose of this work is to evaluate whether 2-oleoyl glycerol (2-OG) improves glucose tolerance through GPR119, using wild type (WT) and GPR 119 knock out (KO) mice. We here show that GPR119 is essential for 2-OG-mediated release of GLP-1 and CCK from GLUTag cells, since a GPR119 specific antagonist completely abolished the hormone release...
June 14, 2016: BioFactors
https://www.readbyqxmd.com/read/27208320/glucose-variability-in-a-26-week-randomized-comparison-of-mealtime-treatment-with-rapid-acting-insulin-versus-glp-1-agonist-in-participants-with-type-2-diabetes-at-high-cardiovascular-risk
#9
(no author information available yet)
OBJECTIVE: A1C is associated with diabetes complications but does not reflect glycemic variability (GV), which may worsen outcomes by inducing inflammation, oxidative stress, and cardiac arrhythmias. We tested whether a glucagon-like peptide 1 agonist-based regimen can reduce GV and cardiometabolic risk markers while maintaining similar A1C levels in people with insulin-requiring type 2 diabetes and high cardiovascular risk. RESEARCH DESIGN AND METHODS: After run-in on metformin and basal-bolus insulin (BBI), 102 participants continued metformin and basal insulin and were randomized to exenatide dosing before the two largest meals (glucacon-like peptide-1 receptor agonist and insulin [GLIPULIN group]) or continuation of rapid-acting insulin analogs (BBI group)...
June 2016: Diabetes Care
https://www.readbyqxmd.com/read/27179248/cardiovascular-side-effects-and-insulin-secretion-after-intravenous-administration-of-radiolabeled-exendin-4-in-pigs
#10
Anneli Rydén, Görel Nyman, Lovisa Nalin, Susanne Andreasson, Olle Korsgren, Olof Eriksson, Marianne Jensen-Waern
INTRODUCTION: Radiolabeled Exendin-4, a synthetic glucagon-like peptide-1 (GLP-1) analog, is used as a tracer for diagnostic purposes of β-cells and in experimental animal research. Exendin-4 can be radiolabeled with (68)Ga, (111)In or (99m)Tc and used for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging to diagnose insulinomas, visualization of pancreatic β-cell mass and transplanted Islets of Langerhans. In humans, Exendin-4 is widely used as a therapeutic agent for treatment of type 2 diabetes (T2D)...
July 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27163772/protective-effect-of-a-glp-1-analog-on-ischemia-reperfusion-induced-blood-retinal-barrier-breakdown-and-inflammation
#11
Andreia Gonçalves, Cheng-Mao Lin, Arivalagan Muthusamy, Carlos Fontes-Ribeiro, António F Ambrósio, Steven F Abcouwer, Rosa Fernandes, David A Antonetti
PURPOSE: Inflammation associated with blood-retinal barrier (BRB) breakdown is a common feature of several retinal diseases. Therefore, the development of novel nonsteroidal anti-inflammatory approaches may provide important therapeutic options. Previous studies demonstrated that inhibition of dipeptidyl peptidase-IV, the enzyme responsible for the degradation of glucagon-like peptide-1 (GLP-1), led to insulin-independent prevention of diabetes-induced increases in BRB permeability, suggesting that incretin-based drugs may have beneficial pleiotropic effects in the retina...
May 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27062006/glucagon-like-peptide-1-analogs-and-their-effects-on-pancreatic-islets
#12
REVIEW
Eva Tudurí, Miguel López, Carlos Diéguez, Angel Nadal, Rubén Nogueiras
Glucagon-like peptide 1 (GLP-1) exerts many actions that improve glycemic control. GLP-1 stimulates glucose-stimulated insulin secretion and protects β cells, while its extrapancreatic effects include cardioprotection, reduction of hepatic glucose production, and regulation of satiety. Although an appealing antidiabetic drug candidate, the rapid degradation of GLP-1 by dipeptidyl peptidase 4 (DPP-4) means that its therapeutic use is unfeasible, and this prompted the development of two main GLP-1 therapies: long-acting GLP-1 analogs and DPP-4 inhibitors...
May 2016: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/27049466/synergy-between-g%C3%AE-z-deficiency-and-glp-1-analog-treatment-in-preserving-functional-%C3%AE-cell-mass-in-experimental-diabetes
#13
Allison L Brill, Jaclyn A Wisinski, Mark T Cadena, Mary F Thompson, Rachel J Fenske, Harpreet K Brar, Michael D Schaid, Renee L Pasker, Michelle E Kimple
A defining characteristic of type 1 diabetes mellitus (T1DM) pathophysiology is pancreatic β-cell death and dysfunction, resulting in insufficient insulin secretion to properly control blood glucose levels. Treatments that promote β-cell replication and survival, thus reversing the loss of β-cell mass, while also preserving β-cell function, could lead to a real cure for T1DM. The α-subunit of the heterotrimeric Gz protein, Gαz, is a tonic negative regulator of adenylate cyclase and downstream cAMP production...
May 2016: Molecular Endocrinology
https://www.readbyqxmd.com/read/26935087/-regulation-of-lipid-metabolism-by-diacylglycerol-kinases-in-pancreatic-%C3%AE-cells
#14
Yukiko K Kaneko, Tomohisa Ishikawa
The appropriate secretion of insulin from pancreatic β-cells is essential for regulating blood glucose levels. Glucose-stimulated insulin secretion (GSIS) involves the following steps: Glucose uptake by pancreatic β-cells is metabolized to produce ATP. Increased ATP levels result in the closure of ATP-sensitive K(+) (KATP) channels, resulting in membrane depolarization that activates voltage-dependent Ca(2+) channels to subsequently trigger insulin secretion. In addition to this primary mechanism through KATP channels, insulin secretion is regulated by cyclic AMP and diacylglycerol (DAG), which mediate the effects of receptor agonists such as GLP-1 and acetylcholine...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/26901633/glucocorticoids-inhibit-basal-and-hormone-induced-serotonin-synthesis-in-pancreatic-beta-cells
#15
Moina Hasni Ebou, Amrit Singh-Estivalet, Jean-Marie Launay, Jacques Callebert, François Tronche, Pascal Ferré, Jean-François Gautier, Ghislaine Guillemain, Bernadette Bréant, Bertrand Blondeau, Jean-Pierre Riveline
Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line...
2016: PloS One
https://www.readbyqxmd.com/read/26807509/hepatic-adenylate-cyclase-3-is-upregulated-by-liraglutide-and-subsequently-plays-a-protective-role-in-insulin-resistance-and-obesity
#16
Y Liang, Z Li, S Liang, Y Li, L Yang, M Lu, H F Gu, N Xia
OBJECTIVE: Recent studies have demonstrated that adenylate cyclase 3 (AC3) has a protective role in obesity. This gene resides at the pathway with glucagon-like peptide (GLP)-1. Liraglutide is a GLP-1 analog and has independent glucose and body weight (BW)-reducing effects. In the present study, we aimed to examine whether hepatic AC3 activity was regulated by Liraglutide and to further understand the effect of AC3 in reduction of BW and insulin resistance. SUBJECTS: The diabesity and obese mice were induced from db/db and C57BL/6 J mice, respectively, by high-fat diet...
2016: Nutrition & Diabetes
https://www.readbyqxmd.com/read/26794660/inhibition-of-the-map3-kinase-tpl2-protects-rodent-and-human-%C3%AE-cells-from-apoptosis-and-dysfunction-induced-by-cytokines-and-enhances-anti-inflammatory-actions-of-exendin-4
#17
E M Varin, A Wojtusciszyn, C Broca, D Muller, M A Ravier, F Ceppo, E Renard, J-F Tanti, S Dalle
Proinflammatory cytokines exert cytotoxic effects on β-cells, and are involved in the pathogenesis of type I and type II diabetes and in the drastic loss of β-cells following islet transplantation. Cytokines induce apoptosis and alter the function of differentiated β-cells. Although the MAP3 kinase tumor progression locus 2 (Tpl2) is known to integrate signals from inflammatory stimuli in macrophages, fibroblasts and adipocytes, its role in β-cells is unknown. We demonstrate that Tpl2 is expressed in INS-1E β-cells, mouse and human islets, is activated and upregulated by cytokines and mediates ERK1/2, JNK and p38 activation...
2016: Cell Death & Disease
https://www.readbyqxmd.com/read/26768240/cardiovascular-effects-of-incretin-based-therapies
#18
William B White, William L Baker
The incretin-based therapies, dipeptidyl peptidase-4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1) analogs, are important new classes of therapy for type 2 diabetes mellitus (T2DM). These agents prolong the action of the incretin hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), by inhibiting their breakdown. The incretin hormones improve glycemic control in T2DM by increasing insulin secretion and suppressing glucagon levels. The cardiovascular (CV) effects of the incretin-based therapies have been of substantial interest since 2008, when the US Food and Drug Administration began to require that all new therapies for diabetes undergo rigorous assessment of CV safety through large-scale CV outcome trials...
2016: Annual Review of Medicine
https://www.readbyqxmd.com/read/26655062/controlled-release-of-biologics-for-the-treatment-of-type-2-diabetes
#19
REVIEW
Caslin A Gilroy, Kelli M Luginbuhl, Ashutosh Chilkoti
Type 2 diabetes is a rapidly growing disease that poses a significant burden to the United States healthcare system. Despite the many available treatments for the disease, close to half of diagnosed type 2 diabetes cases are not properly managed, largely due to inadequate patient adherence to prescribed treatment regimens. Methods for improving delivery - and thereby easing administration - of type 2 drugs have the potential to greatly improve patient health. This review focuses on two peptide drugs - insulin and glucagon-like peptide 1 (GLP-1) - for treatment of type 2 diabetes...
October 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/26548422/the-importance-of-postprandial-glycemic-control-optimizing-add-on-therapy-to-basal-insulin
#20
REVIEW
Charles F Shaefer, John Anderson
Diabetes, mainly type 2 diabetes mellitus (T2DM), is associated with a growing clinical and economic burden in the United States, which is expected to increase in association with an aging population. Sufficient glycemic control in patients with T2DM, in order to reduce the risk of micro- and macrovascular complications associated with diabetes, is mediated by lifestyle modifications and a regimen of increasingly intensive antidiabetes drugs. Several treatments and strategies are available for primary care physicians to select from when choosing the most appropriate therapy for their individual patients with T2DM, but, ultimately, due to the progressive nature of the disease, most of these patients will require insulin therapy to maintain glycemic control...
January 2016: Postgraduate Medicine
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