LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29662071.
- Also identified by DOI 10.1038/s41467-018-03943-0 and PMC identifier 5902555.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis. Here, we show that BL001, a small LRH-1 agonist, impedes hyperglycemia progression and the immune-dependent inflammation of pancreas in murine models of T1DM, and beta cell apoptosis in islets of type 2 diabetic patients, while increasing beta cell mass and insulin secretion. Thus, we suggest that LRH-1 agonism favors a dialogue between immune and islet cells, which could be druggable to protect against diabetes mellitus.
Medical subject headings
- Cell Communication
- Diabetes Mellitus, Experimental
- Hypoglycemic Agents
- Insulin-Secreting Cells
- Phenalenes
- Receptors, Cytoplasmic and Nuclear