Molecules, Vol. 24, Pages 2870: Discovery of Novel DPP-IV Inhibitors as Potential Candidates for the Treatment of Type 2 Diabetes mellitus Predicted by 3D QSAR Pharmacophore Models, Molecular Docking and de novo Evolution

In this study, the predicted compounds were suggested as potent anti-diabetic candidates. Chosen structures were applied following computational strategies: The generation of the three-dimensional quantitative structure-activity relationship (3D QSAR) pharmacophore models, virtual screening, molecular docking, and de novo Evolution. The method also validated by performing re-docking and cross-docking studies of seven protein systems for which crystal structures were available for all bound ligands. The molecular docking experiments of predicted compounds within the binding pocket of DPP-IV were conducted. By using 25 training set inhibitors, ten pharmacophore models were generated, among which hypo1 was the best pharmacophore model with the best predictive power on account of the highest cost difference (352.03), the lowest root mean squared deviation (RMSD) (2.234), and the best correlation coefficient (0.925). Hypo1 pharmacophore model was used for virtual screening. A total of 161 compounds including 120 from the databases, 25 from the training set, 16 from the test set were selected for molecular docking. Analyzing the amino acid residues of the ligand-receptor interaction, it can be concluded that Arg125, Glu205, Glu206, Tyr547, Tyr662, and Tyr666 are the main amino acid residues. The last step in this study was de novo Evolution that generated 11 novel compounds. The derivative dpp4_45_Evo_1 by all scores CDOCKER_ENERGY (CDOCKER, -41.79), LigScore1 (LScore1, 5.86), LigS...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research

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In this study we evaluated if the intake of an oleuropein-enriched chocolate could have positive effects on glycaemia and insulin levels in patients with type 2 diabetes mellitus (T2DM) and healthy subjects (HS).
Source: Clinical Nutrition - Category: Nutrition Authors: Tags: Original article Source Type: research
Publication date: Available online 23 July 2019Source: Nutrition, Metabolism and Cardiovascular DiseasesAuthor(s): Barchetta I, Ciccarelli G, Barone E, Cimini FA, Ceccarelli V, Bertoccini L, Sentinelli F, Tramutola A, Del Ben M, Angelico F, Baroni MG, Lenzi A, Cavallo MGAbstractBackgroundDipeptidyl peptidase 4 (DPP4) is a key enzyme involved in the regulation of the incretin system exerted by cleaving the glucagon-like peptide 1 (GLP-1); the blockage of DPP4, exerted by the antidiabetic agents DPP4-inhibitors (DPP4-I), results in greater GLP-1 concentration and improved glycaemic control. DPP4 acts also as a pro-inflammato...
Source: Nutrition, Metabolism and Cardiovascular Diseases - Category: Nutrition Source Type: research
CONCLUSION: While dietary fiber did not induce additional changes in glycemic parameters, it showed a trend of improvement in insulin sensitivity in 'responders.' Even if patients are already receiving diabetes treatment, the additional administration of fiber can lead to additional benefits in the treatment of diabetes. PMID: 31237126 [PubMed - as supplied by publisher]
Source: Diabetes and Metabolism Journal - Category: Endocrinology Tags: Diabetes Metab J Source Type: research
ConclusionsThis meta-analysis demonstrated that GLP-1RAs were associated with a significant reduction in major adverse CV events, CV death, stroke and death from any cause, while DPP-4 inhibitors were comparable to placebo for all CV outcomes, including hospitalizations for heart failure.RésuméObjectifsLes auteurs de deux grands essais randomisés ont récemment publié leurs conclusions concernant les effets d'un agoniste du récepteur au glucagon-like peptide-1 (A-GLP-1R) (essai HARMONY) et d'un inhibiteur de la dipeptidyl peptidase 4 (DPP-4) (essai CARMELINA) sur les b&eac...
Source: Canadian Journal of Diabetes - Category: Endocrinology Source Type: research
ConclusionIn this pooled analysis of 10,058 patients among studies comparing exenatide with other glucose-lowering medications or placebo, pancreatitis was rare. The EAIRs of pancreatitis were low and similar between exenatide and non-exenatide treatment groups. No evidence of an association between exenatide and pancreatitis was observed.FundingBristol-Myers Squibb and AstraZeneca.Plain Language SummaryPlain language summary available for this article.
Source: Diabetes Therapy - Category: Endocrinology Source Type: research
ConclusionOur results suggest that dulaglutide is an appropriate therapeutic option for patients with T2DM across a wide range of baseline HbA1c values, including those with poor metabolic control.FundingEli Lilly and Company.Plain Language SummaryPlain language summary available for this article.
Source: Diabetes Therapy - Category: Endocrinology Source Type: research
CONCLUSION: The significant potency and appreciable safety of GLP-1 RAs manifested their potential as a logical approach for the management of type 2 diabetes. PMID: 31057118 [PubMed - as supplied by publisher]
Source: Current Diabetes Reviews - Category: Endocrinology Authors: Tags: Curr Diabetes Rev Source Type: research
Abstract T1R3 protein, the main subunit of the sweet taste receptor and receptor of amino acid taste, is expressed in the epithelium of the tongue and gastrointestinal tract, in β cells of the pancreas, hypothalamus, and numerous other organs. Recently, convincing evidences on the involvement of T1R3 in the control of carbohydrate and lipid metabolism, and the control of incretin and insulin production were obtained. In the study on Tas1r3-gene knockout mouse strain and parent C57BL/6J strain as a control, the data on the effect of T1R3 on morphological characteristics of Langerhans islets in the pancreas wer...
Source: Doklady Biological Sciences - Category: Biology Authors: Tags: Dokl Biol Sci Source Type: research
From the Incretin Concept and the Discovery of GLP-1 to Today's Diabetes Therapy Jens Juul Holst* Department of Biomedical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Researchers have been looking for insulin-stimulating factors for more than 100 years, and in the 1960ties it was definitively proven that the gastrointestinal tract releases important insulinotropic factors upon oral glucose intake, so-called incretin hormones. The first significant factor identified was the duodenal glucose-dependent insulinotropic polypeptide, GIP, wh...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Publication date: Available online 23 April 2019Source: Diabetes &Metabolic Syndrome: Clinical Research &ReviewsAuthor(s): Azza Khalifa Bin Hussain, Elamin Abdelgadir, Fauzia Rashid, Abeer Al Haj, Puja Thadani, Alaaeldin M.K. BashierAbstractFor more than a century, the high occurrences of coronary and peripheral artery diseases in diabetes mellitus patients has been well recognised; despite that, the ability to improve CV event rates by optimizing glycaemic control has remained elusive. Nevertheless, the last decade has seen several cardiovascular outcome clinical trials (CVOTs) of many antihyperglycemic agents tha...
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - Category: Endocrinology Source Type: research
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