-The-metabolite-profiles-suggest-that-both-DPPIV-and-NEP-are-also-involved-in-the-in-vivo-degradation-of-liraglutide-g

Seebio semaglutide results of intact liraglutide excreted in urine and feces and the low levels of metabolites in plasma indicate that liraglutide is Absence of QTc prolongation in a thorough QT study with subcutaneous liraglutide, a once-daily human GLP-1 analog for treatment of type 2 diabetes.The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebo-controlled, double-blind crossover study, 51 healthy participants were administered placebo, 0, 1, and 1 mg liraglutide once daily for 7 days each. Electrocardiograms were recorded periodically over 24 hours at the end of placebo and highest dosing periods. Four different models for QT correction were used: QTci, as the primary endpoint, and QTciL, QTcF, and QTcB as secondary endpoints. The upper bound of the 1-sided 95% confidence interval for time-matched, baseline-corrected, placebo-subtracted QTc intervals was <10 ms for all 4 correction methods.

Moxifloxacin (400 mg) increased QTc intervals by 10 to 12 ms at 2 hours. There was no concentration-exposure dependency on QTc interval changes by liraglutide and no QTc thresholds above 500 ms or QTc increases >60 ms. The authors conclude that liraglutide caused no clinically relevant increases in the 10760/cma.j.issn376-2491012216.[Effects of glucagon-like peptide 1(9-36) on endothelial nitric oxide synthase in human umbilical vein endothelial cells].OBJECTIVE: To explore the effects of glucagon-like peptide 1 (GLP-1(9-36)) on endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial METHODS: HUVEC cultured under the conditions of normal glucose (5 mmol/L) or high glucose (16 mmol/L) were incubated with 5-5000 pmol/L GLP-1(9-36).

NO production was assayed by the nitrate reductase method. The eNOS activities were detected by NOS assay kit, p-eNOS (ser-1177) level and total eNOS protein level by Western blot and eNOS mRNA level by real-time reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: Under normal glucose condition, NO productions from HUVEC of 50 - 5000 pmol/L GLP-1(9-36) groups were significantly higher than the control ((41 ± 8) µmol/L vs (22 ± 2) µmol/L, P < 05). So were eNOS activities in cells (16 ± 02 vs 10 ± 00, P < 05). Compared with the control group, the levels of eNOS phosphorylation at ser-1177, mRNA and total protein were significantly elevated in the 5000 pmol/L GLP-1(9-36) group. Under high glucose condition, GLP-1(9-36) retained all the above effects.CONCLUSION: GLP-1 (9-36) can increase NO release, eNOS activity and expression in HUVEC.

This may be one of the underlying mechanisms for the protective effects of GLP-1(9-36) on cardiovascular system.Effect of three different injection sites on the pharmacokinetics of the once-daily human GLP-1 analogue liraglutide.472. Am J Manag Care. 2014 Jul;20(10 Spec No):E12.Can early use of insulin, GLP-1 halt diabetes progression?Effect of peripherally-injected glucagon-like peptide-1 on gastric mucosal blood The aim of this study was to investigate the mechanisms involved in the effect of glucagon-like peptide-1 (GLP-1) on the decrease in gastric mucosal blood flow (GMBF) induced by intragastric ethanol. After preparation of the stomach for GMBF recording, a probe was placed to the gastric mucosa and basal GMBF recordings were obtained by a laser Doppler flowmeter after a 30-minute stabilization period.

Following GLP-1 (1000 ng/kg; i.p.) injection, 1 ml of absolute ethanol was applied to the gastric chamber and GMBF was recorded continuously during a 30-minute period. GLP-1 (1000 ng/kg; i.p.) prevented the decrease in GMBF induced by ethanol. Nitric oxide (NO) synthase inhibitor L-NAME, (30 mg/kg; s.

c.), calcitonine gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (10 microg/kg; i.p.), and cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.) all inhibited the GMBF-improving effect of GLP-1. We concluded that, NO, CGRP and prostaglandins may be involved in the effect of peripherally-injected GLP-1 on GMBF reduction induced by intraluminal ethanol.

10016/j.jdiacomp012518. Epub 2012 Jun 23.Vesiculopustular dermatosis: an uncommon side-effect of liraglutide?Liraglutide is a GLP-1 receptor agonist, a novel medication for type 2 diabetes. We describe a case of pustules in a patient recently started on liraglutide. glp 1 drug of liraglutide are gastrointestinal disorders. Skin and tissue reactions are less well-known side effects.

Liraglutide could be the cause of skin eruptions in this patient, possibly by immunogenicity.Microwave-assisted solid phase synthesis, PEGylation, and biological activity studies of glucagon-like peptide-1(7-36) amide.The insulinotropic hormone glucagon-like peptide-1 (GLP-1) is rapidly inactivated in the body. In order to improve its stability, we replaced the firstly. Then the modified peptide was further PEGylated at thiol group of Cys(30). Biological activity studies showed that the resulting maintaining moderate glucose-lowering activity.Influence of selective fluorination on the biological activity and proteolytic The relative simplicity and high specificity of peptide therapeutics has fueled recent interest.