The impact of GLP-1 receptor agonist shortages on glycaemic Control: Findings from an Australian specialist diabetes clinic
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I write in reply to your article ‘A&E bears brunt of dentist shortages’ (news October 26). The article implies the problem is simply a shortage of dentists, but this is not the whole story.
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Cyclic constraints are incorporated into an 11-residue analogue of the N-terminus of glucagon-like peptide-1 (GLP-1) to investigate effects of structure on agonist activity. Cyclization through linking side chains of residues 2 and 5 or 5 and 9 produced agonists at nM concentrations in a cAMP assay. 2D NMR and CD spectra revealed an N-terminal β-turn and a C-terminal helix that differentially influenced affinity and agonist potency. These structures can inform development of small molecule agonists of the GLP-1 receptor to treat type 2 diabetes.
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Cyclic peptide
Structure–activity relationship
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The Royal Society has issued, in December 1969, a slim pamphlet with the title The Shortage of Mathematics and Science Teachers in Schools. It is a report of a working party composed of representatives of the Royal Society, the Council of Engineering Institutions and the Council of Science and Technology Institutes.
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Combination approaches for the treatment of metabolic diseases such as obesity and diabetes are becoming increasingly relevant. Co-administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist with a cholecystokinin receptor-1 (CCKR1) agonist exert synergistic effects on weight loss in obese rodents. Here, we report on the effects of a novel fusion peptide (C2816) comprised of a stabilized GLP-1R agonist, AC3174, and a CCKR1-selective agonist, AC170222. C2816 was constructed such that AC3174 was linked to the N-terminus of AC170222, thus preserving the C-terminal amide of the CCK moiety. In functional in vitro assays C2816 retained full agonism at GLP-1R and CCKR1 at lower potency compared to parent molecules, whereas a previously reported fusion peptide in the opposite orientation, (pGlu-Gln)-CCK-8/exendin-4, exhibited no activity at either receptor. Acutely, in vivo, C2816 increased cFos in key central nuclei relevant to feeding behavior, and reduced food intake in wildtype (WT), but less so in GLP-1R-deficient (GLP-1RKO), mice. In sub-chronic studies in diet-induced obese (DIO) mice, C2816 exerted superior reduction in body weight compared to co-administration of AC3174 and AC170222 albeit at a higher molar dose. These data suggest that the synergistic pharmacological effects of GLP-1 and CCK pathways can be harnessed in a single therapeutic peptide.
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Treatment with LY3298176, a novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist, resulted in better glucose control than dulaglutide, a GLP-1 receptor agonist, reported a phase 2 trial in the Lancet.
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An Education and Training Board should be set up to deal with skill shortages in new technologies, according to the House of Lords Select Committee on Science and Technology. The Board would have responsibilities for assessing and forecasting the UK's skill needs in the short and long terms, and for ensuring that these needs are met.
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In order to establish high throughout screening method for identifying agonists for glucagon-like petide-1 receptor(GLP-1R),a cell line was set up after the GLP-1 receptor plasmid(GLP-1R/pCDNA3.1) and reporter gene plasmid(3×CRE/3×MRE/SRE-LUC/ pGL3)were co-transfectted CHO at the ratio of 1∶5.To identify and optimize the screening model,the effects of some factors were examined by using GLP-1,such as cell number per well,incubation time,dosage of Bright-GloTM and concentration of DMSO.Based on a steady cell line,a reliable screening model was established for GLP-1R agonist screening.The Z′-factor value for the screening model was estimated 0.75 under the conditions that 4×104 cells in each well were incubated for 8h using 4 times diluted Bright-GloTM and less than 1% DMSO.The extracts of tradition Chinese medicine were assayed using the screening model,and five samples of them showed activity.Experiments showed that this method could be applied to high throughout screen agonist for GLP-1 receptor.
High-Throughput Screening
Glucagon receptor
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The UK is believed to suffer from a shortage of scientists and engineers, yet unemployment rates for new graduates in these fields are high. Does that mean the skills shortage doesn't exist, asks Margaret Harris.
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IN BRIEF The glucagon-like peptide-1 (GLP-1) receptor agonist class of medications has distinct benefits and limitations that provide an opportunity to individualize the treatment of patients with type 2 diabetes. Many strategies can be used to improve patient acceptance of and self-management with a GLP-1 receptor agonist.
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The July issue of Physics Bulletin contained a letter from a schoolmaster drawing attention to the present shortage of physics teachers. It would be difficult to exaggerate the serious nature, or the urgency, of this problem.
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