Design, Synthesis, and Pharmacological Evaluation of Potent Positive Allosteric Modulators of the Glucagon-like Peptide-1 Receptor (GLP-1R).

The therapeutic success of peptidic GLP-1 receptor agonists for treatment of type 2 diabetes mellitus (T2DM) motivated our search for orally bioavailable small molecules that can activate the GLP-1 receptor (GLP-1R) as a well-validated target for T2DM. Here, the discovery and characterization of a potent and selective positive allosteric modulator (PAM) for GLP-1R based on a 3,4,5,6-tetrahydro-1-1,5-epiminoazocino[4,5-]indole scaffold is reported. Optimization of this series from HTS was supported by a GLP-1R ligand binding model.

Since 2015 the SinoGerman research project SIGN supports water quality improvement in the Taihu region, China.

The Taihu (Tai lake) region is one of the most economically prospering areas of China. Due to its location within this district of high anthropogenic activities, Taihu represents a drastic example of water pollution with nutrients (nitrogen, phosphate), organic contaminants and heavy metals. High nutrient levels combined with very shallow water create large eutrophication problems, threatening the drinking water supply of the surrounding cities.

Effect of insulin analogues on phosphatidyl inositol-3 kinase/Akt signalling in INS-1 rat pancreatic derived β-cells.

Context: Insulin analogues are largely used for the treatment of diabetic patients, but concerns have been raised about their mitogenic/anti-apoptotic potential. It is therefore important to evaluate these analogues in different cell systems.

Objective: The aim of this work was to establish the pharmacological profiles of insulin analogues towards PI-3 kinase/Akt pathway in INS-1 β-pancreatic cells.

Development of a conditionally immortalized human pancreatic β cell line.

Diabetic patients exhibit a reduction in β cells, which secrete insulin to help regulate glucose homeostasis; however, little is known about the factors that regulate proliferation of these cells in human pancreas. Access to primary human β cells is limited and a challenge for both functional studies and drug discovery progress. We previously reported the generation of a human β cell line (EndoC-βH1) that was generated from human fetal pancreas by targeted oncogenesis followed by in vivo cell differentiation in mice.