In situ pharmacological induction of pancreatic beta-cell regeneration by THR-123, a cyclic peptide with BMP-7-like activity

ABSTRACT: The demonstration that BMP signaling activates progenitor-like populations within pancreatic ducts supports the potential use of BMP receptor agonists to induce islet regeneration in situ. In this context, we tested the ability of THR-123, a cyclic peptide with BMP-7-like activity, to restore b-cell mass in diabetic mice. Here we show that treatment with THR-123 restores normoglycemia through the rapid formation of new BrdU-labeled islets in the vicinity of ducts. Neogenic islets, unlike those from non-diabetic controls, feature an extensive intrainsular network of ductal tissue. The earlier stages of THR-123-induced b-cell neogenesis were reproduced in live pancreatic slices, an organotypic model that allowed us to visualize ductal cells transitioning to glucose-responsive insulin-expressing cells in real time. scRNAseq analyses further confirmed that this transition occurs through a hybrid ducto-acinar stage similar to that previously reported in humans. These results pave the way to the design of pharmacological strategies to treat insulin-dependent diabetes.

ORGANISM(S): Mus musculus

PROVIDER: GSE274591 | GEO | 2025/06/12

REPOSITORIES: GEO