Chronic GIPR agonism results in pancreatic islet GIPR functional desensitisation.

Objectives: There is renewed interest in targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) for treatment of obesity and type 2 diabetes. G-protein coupled receptor desensitisation is suggested to reduce the long-term efficacy of glucagon-like-peptide 1 receptor (GLP-1R) agonists and may similarly affect the efficacy of GIPR agonists. We explored the extent of pancreatic GIPR functional desensitisation with sustained agonist exposure.

Predicting Immune Flares in Untreated Chronic Hepatitis B Patients Using Novel Risk Factors and the FLARE-B Score.

Background And Aims: Risk factors of chronic hepatitis B (CHB) immune flares are poorly understood. The primary aim of this study was to discover predictors of the CHB flare in non-cirrhotic, untreated CHB patients and develop a simple risk-stratifying score to predict the CHB flare. The secondary aim was to compare different machine learning methods for prediction.

Poly-Dha Sequences as -polypeptides: An Original Mechanistic Postulate Leads to the Discovery of a Long-Acting Vasodilator KU04212.

The construction of polypeptides was revolutionized by Merrifield's solid-phase synthesis more than half a century ago. Herein, we explore a completely different approach to making peptides. We test an original mechanistic postulate wherein a single peptide made entirely of dehydroalanine (Dha) residues can give rise to regio- and stereodefined peptides by iterative conjugate addition of one- or two-electron nucleophiles.