Enhancing insulin secretion by pancreatic β-cell redifferentiation: a study of the anti-diabetic effects of berberine in vitro

The β-cell dedifferentiation and impaired glucose-stimulated insulin secretion (GSIS) contribute to the pathogenesis of diabetes. Berberine (BBR), a natural compound with known anti-diabetic therapeutic properties, has been investigated for its potential role in preserving β-cell function. This study aims to elucidate the molecular mechanism by which BBR prevents β-cell dedifferentiation and restores deteriorated GSIS. In this <i>in vitro</i> study, the MIN-6 and INS-1 pancreatic β-cell lines were exposed to a FoxO1 inhibitor, excessive levels of H₂O₂ or free fatty acids (FFAs) to induce dedifferentiation and impaired GSIS. BBR treatment was administered to assess its impact on β-cell fate and function. Molecular analyses, including gene expression profiling and pathway analysis, were conducted to unravel the underlying molecular mechanisms. BBR treatment significantly reduced β-cell dedifferentiation induced by FoxO1 inhibitor, H₂O₂ and FFAs. BBR treatment effectively reversed the poor GSIS observed under the FoxO1 inhibition and high concentrations of H₂O₂ and FFAs, restored the ability of β cells to respond normally to glucose by secreting insulin. The protective effect was associated with the modulation of nuclear factor kappa B (NF-κB) signaling pathway, while BBR reduced the overproduction of NF-κB, which has been proved by applying NF-κB angoist in INS-1 cell line. This study explored the protective potential of BBR in preventing β-cell dedifferentiation and restoring impaired GSIS, under the conditions of FoxO1 inhibition, excessive levels of H₂O₂ and FFAs. BBR may therefore be a promising candidate for diabetes treatment. <i>In-vivo</i> experiments are warranted to evaluate dedifferentiation levels in rodent diabetic models and the efficacy of BBR on the pancreatic β-cell redifferentiation in diabetes.