GIP metabolite [GIP (3-42)] and GLP-1 metabolite [GLP-1 (9-36) amide] have been reported to differ with regard to biological actions

semaglutide -4 inhibition can therefore reveal different actions of GIP and GLP-1. In catheter wearing Wistar rats, insulinotropic effects of equipotent doses of GIP (2 nmol/kg) and GLP-1 (7-36) amide (4 nmol/kg) and vehicle were tested in the absence/presence of DPP-4 inhibition.  glp 1 agonist  and insulin were frequently sampled. DPP-4 inhibitor was given at -20 min, the incretin at -5 min and the intravenous glucose tolerance test (0 g glucose/kg) commenced at 0 min. G-AUC and I-AUC, insulinogenic index and glucose efflux, were calculated from glucose and insulin curves. Systemic DPP-4 inhibition potentiated the acute GIP incretin effects: I-AUC (115±34 vs.

153±39 ng·min/ml), increased the insulinogenic index (04±04 vs. 09±06 ng/mmol), and improved glucose efflux (19±3 vs. 20±5 min⁻¹). The GLP-1 incretin effects were diminished: I-AUC (124±18 vs. 106±38 ng·min/ml), the insulinogenic index was decreased (00±08 vs. 00±09 ng/mmol), and glucose efflux declined (14±3 vs. 11±3 min⁻¹).

GLP-1 and GIP differ remarkably in their glucoregulatory actions in healthy rats when DPP-4 is inhibited. These previously unrecognized actions of DPP-4 inhibitors could have implications for future use in humans.A DPP-IV-resistant triple-acting agonist of GIP, GLP-1 and glucagon receptors with potent glucose-lowering and insulinotropic actions in high-fat-fed mice.University of Ulster, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, UK.AIMS/HYPOTHESIS: We designed a chemically modified, enzyme-resistant peptide with triple-acting properties based on human glucagon with amino acid substitutions aligned to strategic positions in the sequence of glucose-dependent insulinotropic polypeptide (GIP).YAG-glucagon) was incubated with dipeptidylpeptidase IV (DPP-IV) to assess stability, BRIN-BD11 cells to evaluate insulin secretion, and receptor-transfected cells to examine cAMP production. Acute glucose-lowering and insulinotropic properties of YAG-glucagon were assessed in National Institutes of Health (NIH) Swiss mice, while longer-term actions on glucose homeostasis, insulin secretion, food intake and body weight were examined in RESULTS: YAG-glucagon was resistant to DPP-IV, increased in vitro insulin secretion (1-3-fold; p < 001) and stimulated cAMP production in GIP receptor-, glucagon-like peptide-1 (GLP-1) receptor- and glucagon receptor-transfected cells.

Plasma glucose levels were significantly reduced (by 51%; p < 01) and insulin concentrations increased (1-fold; p < 01) after acute injection of YAG-glucagon in NIH Swiss mice. Acute actions were countered by established GIP, GLP-1 and glucagon antagonists. In high-fat-fed mice, twice-daily administration of YAG-glucagon for 14 days reduced plasma glucose (40% reduction; p < 01) and increased plasma insulin concentrations (1-fold; p < 05). Glycaemic responses were markedly improved (19-48% reduction; p < 05) and insulin secretion enhanced (1-fold; p < 05) after a glucose load, which were independent of changes in insulin sensitivity, food intake and body CONCLUSIONS/INTERPRETATION: YAG-glucagon is a DPP-IV-resistant triple agonist of GIP, GLP-1 and glucagon receptors and exhibits beneficial biological properties suggesting that it may hold promise for treatment of type 2 diabetes.Cardioprotective effects of incretin during ischaemia-reperfusion.Chiang Mai University, Chiang Mai, Thailand.Incretin is a gut derived peptide hormone secreted in the intestine after food ingestion, and is degraded rapidly after secretion by dipeptidyl peptidase (DPP)-4.

Incretin-based therapy, such as glucagon-like peptide (GLP)-1 and the DPP-4 inhibitor, has been proposed as a new therapeutic approach for the treatment of type 2 diabetic patients. In the past few years, growing evidence also demonstrated the cardioprotective effects of incretin-based therapy, especially during ischaemia-reperfusion (I/R) injury in both the animal models and in clinical studies. However, inconsistent reports exist regarding the use of these pharmacological interventions. In this article, a comprehensive review regarding both basic and clinical studies reporting the effects of GLP-1 and DPP-4 inhibitors on I/R hearts is presented and discussed. The consistent findings as well as controversial results are summarised, focusing on the effects of incretin on the infarct size, left ventricular function and haemodynamic improvement during an I/R injury.Sulfono-γ-AApeptides as Helical Mimetics: Crystal Structures and Applications.Avenue, Tampa, Florida 33620, United States.

Foldamers have defined and predictable structures, improved resistance to proteolytic degradation, enhanced chemical diversity, and are versatile in their mimicry of biological molecules, making them promising candidates in biomedical and material applications. However, as natural macromolecules exhibit endless folding structures and functions, the exploration of the applications of foldamers remains crucial. As such, it is imperative to continue to discover unnatural foldameric architectures with new frameworks and molecular scaffolds.