The Beneficial Impact of a Novel Pancreatic Polypeptide Analogue on Islet Cell Lineage

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4215 - 4215

Published: April 29, 2025

(Proline3)PP, or (P3)PP, is an enzymatically stable, neuropeptide Y4 receptor (NPY4R)-selective, pancreatic polypeptide (PP) analogue with established weight-lowering and islet morphology benefits in obesity-diabetes. In the current study, we now investigate impact of twice-daily (P3)PP administration (25 nmol/kg) for 11 days on cell lineage, using streptozotocin (STZ) diabetic Ins1Cre/+;Rosa26-eYFP GluCreERT2;Rosa26-eYFP transgenic mice enhanced yellow fluorescent protein (eYFP) labelling beta-cell alpha-cells, respectively. had no obvious body weight blood glucose levels STZ-diabetic at dose tested, but did return food intake towards control mice. Notably, insulin content was augmented by treatment both mice, alongside area reduced alpha-cell area. Beneficial (P3)PP-induced changes were consistently associated decreased apoptosis, while also proliferation Alpha-cell turnover rates returned healthy intervention mouse models. terms increased transition alpha- to beta-cells as well beta- differentiation shown contribute enhancement (P3)PP-treated Together these data reveal, first time, sustained NPY4R activation positively modulates turnover, plasticity, help preserve architecture following STZ-induced metabolic stress.

Language: Английский

[P³]PP, a stable, long‐acting pancreatic polypeptide analogue, evokes weight lowering and pancreatic beta‐cell‐protective effects in obesity‐associated diabetes

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 26(11), P. 4945 - 4957

Published: Aug. 27, 2024

To thoroughly investigate the impact of sustained neuropeptide Y4 receptor (NPY4R) activation in obesity-associated diabetes.

Language: Английский