Backgrounds: 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. Objectives: The molecular mechanism by which BBR prevents β cell dedifferentiation and restores deteriorated GSIS was carefully examined in the mouse Min6 β cell line. Methods: In this in vitro study, MIN-6 cells were exposed to 10 μM FoxO1 inhibitor-AS1842856 for 24 hours, excessive levels of H2O2 or free fatty acids (FFAs) to induce dedifferentiation and impaired GSIS, mimicking type 2 diabetes. BBR treatment was then administered for 24 hours to assess its impact on β cell fate and function. Molecular analyses were conducted to unravel the underlying molecular mechanisms, including gene expression and signal pathway analysis. Results: BBR treatment significantly reduced β cell dedifferentiation induced by FoxO1 inhibitor, high concentrations of H2O2 and FFA. Such treatment effectively reversed the poor GSIS (30 mins after high glucose treatment) observed in MIN6 cells under the FoxO1 inhibition and the treatments by H2O2 and FFA, and restored the normal response to glucose to release insulin. The protective effect was associated with the reduction of overproduction of NF-κB. This study explored the therapeutic potential of BBR in preventing β-cell dedifferentiation and restoring impaired GSIS, under the conditions of FoxO1 inhibition, excessive levels of H2O2 and FFA. Conclusions: BBR may therefore be a promising candidate for diabetes treatment. In-vivo investigations are warranted to evaluate dedifferentiation levels in rodent diabetic models and the efficacy of BBR on the pancreatic β cell redifferentiation in diabetes.
Work was supported by NHMRC, University of Queensland, and CSC China Scholarship Council.