Nicotinic Signaling Stimulates Glucagon Secretion in Mouse and Human Pancreatic α-Cells.

Smoking is widely regarded as a risk factor for type 2 diabetes because nicotine contributes to insulin resistance by desensitizing the insulin receptors in muscle, liver, or fat. Little is known, however, about the immediate regulation of islet hormonal output by nicotine, an agonist of ionotropic cholinergic receptors. We investigated this by imaging cytosolic Ca2+ dynamics in mouse and human islets using confocal microscopy and measuring glucagon secretion in response to the alkaloid from isolated mouse islets.

The impact of GLP-1 signalling on the energy metabolism of pancreatic islet β-cells and extrapancreatic tissues.

Glucagon-like peptide-1 signalling impacts glucose homeostasis and appetite thereby indirectly affecting substrate availability at the whole-body level. The incretin canonically produces an insulinotropic effect, thereby lowering blood glucose levels by promoting the uptake and inhibiting the production of the sugar by peripheral tissues. Likewise, GLP-1 signalling within the central nervous system reduces the appetite and food intake, whereas its gastric effect delays the absorption of nutrients, thus improving glycaemic control and reducing the risk of postprandial hyperglycaemia.

Dopamine signalling in pancreatic islet cells and role in adaptations to metabolic stress.

Objectives: Dopamine and related receptors are evidenced in pancreatic endocrine tissue, but the impact on islet β-cell stimulus-secretion as well as (patho)physiological role are unclear.

Methods: The present study has evaluated islet cell signalling pathways and biological effects of dopamine, as well as alterations of islet dopamine in rodent models of diabetes of different aetiology.

Key Findings: The dopamine precursor l-DOPA partially impaired glucose tolerance in mice and attenuated glucose-, exendin-4, and alanine-induced insulin secretion.

Integrating multiscale and machine learning approaches towards the SAMPL9 log challenge.

The partition coefficient (log ) is an important physicochemical property that provides information regarding a molecule's pharmacokinetics, toxicity, and bioavailability. Methods to accurately predict the partition coefficient have the potential to accelerate drug design. In an effort to test current methods and explore new computational techniques, the statistical assessment of the modeling of proteins and ligands (SAMPL) has established a blind prediction challenge.