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GLP-1 diabetes

Amin Al-Awar, Nikoletta Almási, Renáta Szabó, Istvan Takacs, Zsolt Murlasits, Gergő Szűcs, Szilvia Török, Anikó Pósa, Csaba Varga, Krisztina Kupai
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral anti-diabetic drugs, implicated in pleiotropic secondary cardioprotective effects. The aim of the study was to unveil the unknown and possible cardioprotective targets that can be exerted by sitagliptin (Sitg) against ischemia-reperfusion (I/R) injury. Male wistar rats received 2 weeks' Sitg oral treatment of different doses (25, 50, 100, and 150 mg/kg/day), or saline as a Control. Hearts were then isolated and subjected to two different I/R injury protocols: 10 min perfusion, 45 min regional ischemia, and 120 min reperfusion for infarct size (IS) measurement, or: 10 min perfusion, 45 min regional ischemia and 10 min reperfusion for biochemical analysis: nitric oxide synthases (NOSs) and DPP-4 activity, glucagon-like peptide-1 (GLP-1), Calcium, transient receptor potential vanilloid (TRPV)-1 and calcitonin gene-related peptide (CGRP) levels, transient receptor potential canonical (TRPC)-1 and e-NOS protein expression...
October 18, 2018: International Journal of Molecular Sciences
A J Scheen, C Mathieu
Xultophy® (IDegLira) is a fixed ratio combination of basal insulin degludec and glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. Insulin degludec is characterized by an original mode of prolonged and continuous insulin diffusion after its subcutaneous injection. Thereby, it has a very long half-life, around 25 hours, and a better reproducibility from both a pharmacokinetic and pharmacodynamic point of view, with less hypoglycaemia, especially at night. Liraglutide is a well-known once-daily GLP-1 receptor agonist that showed a cardiovascular and renal protection in patients with type 2 diabetes at high cardiovascular risk...
October 2018: Revue Médicale de Liège
Thorsten Otto, Melissa Myland, Heike Jung, Jeremie Lebrec, Hartmut Richter, Kirsi Norrbacka
Objective This retrospective database analysis complements previous research to understand treatment patterns for German patients newly initiating or switching to subsequent GLP-1 RAs. Methods Adult patients (≥18 years) initiating GLP-1 RA (Cohort 1 [C1]) or switching from a previous GLP-1 RA (Cohort 2 [C2]) to exenatide twice-daily (exBID), exenatide once-weekly (exQW), dulaglutide (DULA), or liraglutide (LIRA) were included in this analysis using IQVIA LRx from 01/01/2014-31/03/2017. Patients were required to have ≥1 oral antidiabetic prescription during the 6-month pre-index period and ≥12 months follow-up...
October 17, 2018: Current Medical Research and Opinion
J-H Liou, Y-M Liu, C-H Chen
BACKGROUND: Diabetes mellitus (DM) is the major cause of end-stage renal disease (ESRD) in Taiwan. Despite the use of steroids and/or calcineurin inhibitors (CNIs) in renal transplantation (RTx), additional challenges occur when a patient displays persisting metabolic disease, carries on an unhealthy lifestyle, or experiences genetic effects. Although RTx recipients could get better glycemic control by oral anti-diabetic drugs (OADs) or several insulin agents, they still need more than two kinds of medication...
October 2018: Transplantation Proceedings
Daniela Guarino, Diego Moriconi, Andrea Mari, Eleni Rebelos, Daria Colligiani, Simona Baldi, Marco Anselmino, Ele Ferrannini, Monica Nannipieri
AIMS/HYPOTHESIS: Postprandial hypoglycaemia (PPHG) is a complication of Roux-en-Y gastric bypass (RYGB) surgery in normoglycaemic individuals. In type 2 diabetes, RYGB improves glucose metabolism, but whether this improvement is related to the later development of PPHG is not known. We investigated the presence and mechanisms of PPHG in individuals with type 2 diabetes undergoing RYGB. METHODS: A total of 35 obese individuals with type 2 diabetes underwent an OGTT before and 24 months after surgery...
October 12, 2018: Diabetologia
Galyna V Graham, J Michael Conlon, Yasser H Abdel-Wahab, Peter R Flatt
Glucagon-like peptides-1 (GLP-1)from phylogenetically ancient fish (lamprey, dogfish, ratfish, paddlefish and bowfin) and from a teleost, the rainbow trout produced concentration-dependent stimulations of insulin release from clonal β-cells and isolated mouse islets. Lamprey and paddlefish GLP-1 were the most potent and effective. Incubation of BRIN-BD11 cells with GLP-1 receptor (GLP1R) antagonist, exendin-4 (9-39) attenuated insulinotropic activity of all peptides whereas glucagon receptor (GCGR) antagonist [des-His1 ,Pro4 ,Glu9 ] glucagon amide significantly decreased the activities of lamprey and paddlefish GLP-1 only...
October 9, 2018: Molecular and Cellular Endocrinology
Yue Yao, Qiang Li, Wei Wang, Jinchao Zhang, Ping Gao, Yi Xu
BACKGROUND/AIMS: Abnormal regulation of cholesterol homeostasis is associated with type 2 diabetes mellitus (T2DM) and multiple other diseases. Glucagon-like peptide-1 (GLP-1) has unique effects on modulating hepatic lipid metabolism. However, the mechanism behind these is largely unknown. The aim of this study was to investigate the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. METHODS: Cell viability was determined by CCK-8...
October 11, 2018: Cellular Physiology and Biochemistry
Michael Dempsey, Michelle Mocarski, Jakob Langer, Barnaby Hunt
OBJECTIVE: In the DUAL (Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) VII trial, IDegLira (a combination of insulin degludec and liraglutide) was compared with insulin glargine U100 plus insulin aspart. Both treatment approaches achieved similar glycemic control, but there were differences in hypoglycemia, changes in body weight, and injection frequency. The aim of the present analysis was to assess the short-term cost effectiveness of IDegLira versus insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin in the U...
September 2018: Endocrine Practice
O Montvida, J B Green, J Atherton, S K Paul
AIMS: In people with metformin-treated diabetes, to evaluate the risk of acute pancreatitis, pancreatic cancer and other diseases of the pancreas post second-line anti-hyperglycaemic agent initiation. METHODS: People with Type 2 diabetes diagnosed after 2004 who received metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i, n = 50 095), glucagon-like peptide-1 receptor agonist (GLP-1RA, n = 12 654), sulfonylurea (n = 110 747), thiazolidinedione (n = 17 597) or insulin (n = 34 805) for at least 3 months were identified in the US Centricity Electronic Medical Records...
October 10, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Giulio Marchesini, Patrizio Pasqualetti, Roberto Anichini, Salvatore Caputo, Giuseppe Memoli, Paola Ponzani, Veronica Resi, Manfredi Rizzo, Gaetano Serviddio, Giorgio Zanette
AIMS: Several drug classes are now available to achieve a satisfactory metabolic control in patients with type 2 diabetes (T2DM), but patients' preferences may differ. METHODS: In a discrete-choice experiment, we tested T2DM patients' preferences for recent antidiabetic drugs, in the event that their treatment might require intensification. The following attributes were considered: (a) route of administration; (b) type of delivery; (c) timing; (d) risk of adverse events; (e) effects on body weight...
October 10, 2018: Acta Diabetologica
Brandon B Boland, Charles Brown, Michelle L Boland, Jennifer Cann, Michael Sulikowski, Gitte Hansen, Rikke V Grønlund, Wanda King, Cristina Rondinone, James Trevaskis, Christopher J Rhodes, Joseph S Grimsby
The onset of common obesity-linked type 2 diabetes (T2D) is marked by exhaustive failure of pancreatic β-cell functional mass to compensate for insulin resistance and increased metabolic demand, leading to uncontrolled hyperglycemia. Here, the β-cell deficient obese hyperglycemic/hyperinsulinemic KS db/db mouse model was used to assess consequential effects on β-cell functional recovery by lowering glucose homeostasis and/or improving insulin sensitivity following treatment with thiazolidinedione (TZD) therapy or glucagon-like-peptide-1 receptor (GLP-1R) agonism alone, or in combination with sodium/glucose cotransporter-2 inhibition (SGLT-2i)...
October 10, 2018: Diabetes
A M Sørensen, M B Christensen
Type 2 diabetes mellitus is a common and severe chronic metabolic disease, which confers increased risk of cardiovascular disease and mortality. During the last decade a large number of new drugs within the classes dipeptidyl peptidase 4 (DPP-4) inhibitors (DPP-4Is), glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) and sodium/glucose cotransporter 2 (SGLT-2) inhibitors (SGLT-2Is) have been developed and tested in nine large-scale cardiovascular outcome trials (CVOTs). Here we review the evidence behind antihyperglycemic treatment of patients with type 2 diabetes with a particular focus on compiling and summarizing the evidence of hard clinical endpoints stemming from these large CVOTs...
September 2018: Drugs of Today
Koichi Misawa, Hiroko Jokura, Akira Shimotoyodome
Background: Compared to white rice, brown rice induces a lower glycemic response in healthy and diabetic humans. This effect is partly attributed to the higher amounts of water- or oil-soluble bran components and dietary fiber in brown rice. We hypothesized that dietary supplementation with oil-soluble rice bran triterpenoids (RBTs; triterpene alcohol and sterol prepared from rice bran) might reduce the incidence of postprandial hyperglycemia in healthy humans. Objective: We examined the acute effects of a single RBT-supplemented meal on the postprandial blood glucose responses of healthy male adults in a double-blind, randomized, placebo-controlled, crossover trial...
2018: Food & Nutrition Research
Qiuyu Wang, Chunlin Zhao, Lili Jin, Hanyu Zhang, Qifan Miao, Hongsheng Liu, Dianbao Zhang
Diabetes is a metabolic disorder leading to many complications. The treatment of diabetes mainly depends on hypoglycemic drugs, often with side effects, which drive us to develop novel agents. AWRK6 was a peptide developed from the antimicrobial peptide Dybowskin-2CDYa in our previous study, and the availability of AWRK6 on diabetes intervention was unknown. Here, in vivo and in vitro experiments were carried out to investigate the effects of AWRK6 against diabetes. In diabetic mice, induced by high-fat diet followed by streptozocin (STZ) administration, the daily administration of AWRK6 presented acute and sustained hypoglycemic effects...
October 7, 2018: International Journal of Molecular Sciences
Gang Niu, Guohao Wang, Joseph Lau, Lixin Lang, Orit Jacobson, Ying Ma, Dale O Kiesewetter, Shaoliang Zhang, Xiaoyuan Chen
Abextide, synthesized by conjugating an albumin-binding moiety-truncated Evans blue-to glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4, shows extended drug release and enhanced hypoglycemic effect in diabetic mice. The aim of this study is to evaluate the pharmacodynamics of Abextide in nonhuman primates. Two batches of elderly cynomolgus monkeys with naturally occurring diabetes are used for this study. During the whole experiment period, no abnormalities such as swelling at the injection site, lethargy, or hypoglycemia are observed in all animals...
October 9, 2018: Advanced Healthcare Materials
Zhiqiang Cheng, Guozhi Liu, Xiang Zhang, Dongsong Bi, Sanyuan Hu
BACKGROUND Bile acids (BAs) are signaling molecules that participate in maintaining glucose homeostasis. Acute enteral infusion of BAs potently reduces the glycemic response to glucose, associated with an increase of incretin hormones. However, the effect of long-term supplementation of BAs on glucose metabolism has not been fully investigated. MATERIAL AND METHODS Thirty diabetic rats were assigned to a control group (n=10), a low TCA group (L-TCA group, n=10), and a high TCA group (H-TCA group, n=10). Rats in the control group were fed a regular high-fat diet (HFD), while rats in the L-TCA group and H-TCA group were fed a TCA (taurocholic acid)-mixed HFD with the concentrations of 0...
October 9, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Kang-Hoon Kim, In-Seung Lee, Ji Young Park, Yumi Kim, Eun-Jin An, Hyeung-Jin Jang
Taste receptors exist in several organs from tongue to colon and have diverse functions dependent on specific cell type. In enteroendocrine L-cells, stimulation of taste receptor signaling induces incretin hormones. Among incretin hormones, glucagon-like peptide-1 (GLP-1) induces insulinotropic action by activating GLP-1 receptor of pancreatic β-cells. However, GLP-1 mimetic medicines have reported clinical side effects, such as autoimmune hepatitis, acute kidney injury, pancreatitis, and pancreatic cancer...
2018: Frontiers in Pharmacology
John-Michael Gamble, Eugene Chibrikov, William K Midodzi, Laurie K Twells, Sumit R Majumdar
OBJECTIVES: To compare population-based incidence rates of new-onset depression or self-harm in patients initiating incretin-based therapies with that of sulfonylureas (SU) and other glucose-lowering agents. DESIGN: Population-based cohort study. SETTING: Patients attending primary care practices registered with the UK-based Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Using the UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidyl peptidase-4 inhibitor (DPP-4i)-cohort, consisting of new users of DPP-4i and SU and (2) glucagon-like peptide-1 receptor agonists (GLP-1RA)-cohort, consisting of new users of GLP-1RA and SU, between January 2007 and January 2016...
October 8, 2018: BMJ Open
Khyati Girdhar, Budheswar Dehury, Mahender Kumar Singh, Vineeth P Daniel, Abhinav Choubey, Surbhi Dogra, Sunil Kumar, Prosenjit Mondal
The glucagon-like peptide-1 receptor (GLP-1R) is a well-known target of therapeutics industries for the treatment of various metabolic diseases like Type2 Diabetes and Obesity. The structural-functional relationships of small molecule agonists and GLP-1R are yet to be understood. Therefore, an attempt was made on structurally known GLP-1R agonists (Compound 1, Compound 2, Compound A, Compound B, and (S)-8) to study their interaction with the extracellular domain of GLP-1R. In this study, we explored the dynamics, intrinsic stability and binding mechanisms of these molecules through computational modeling, docking, molecular dynamics (MD) simulations and MM/PBSA binding free energy estimation...
October 8, 2018: Journal of Biomolecular Structure & Dynamics
Scott A Coon, Erica F Crannage, Lara C Kerwin, Justinne E Guyton
Semaglutide once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) injection has been approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus (T2DM). Areas Covered: The safety and efficacy of the semaglutide once-weekly injection are reviewed using results from preliminary pharmacology studies and later-phase randomized control trials (RCTs) and meta-analyses. Semaglutide once-weekly is compared to placebo and active comparators for T2DM in the SUSTAIN clinical trial series, with outcomes of: glycemic control, weight loss, major adverse cardiovascular events, and adverse effects...
October 8, 2018: Expert Review of Clinical Pharmacology
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