Fig. 1: BBR increases high-glucose-dependent insulin secretion from pancreatic islets.

a Berberine (BBR) is a plant alkaloid isolated from the Coptidis rhizoma, the dried rhizome of Coptis chinensis. b Viability of the indicated cells incubated with different concentrations of BBR for 30 min. n = 5. c Mouse islets (15 islets per batch) were incubated with low (2.8 mM) or high (25 mM) glucose concentrations in the absence or presence of the indicated concentrations of BBR. The secreted insulin level in the supernatant was normalized to the corresponding insulin content of the islets. n = 5. P = 0.0417 for 5 μM BBR, P = 0.0297 for 25 μM BBR under 25 mM glucose concentration. Statistical significance was assessed using one-way ANOVAs coupled with Dunnett’s post-hoc test (two-sided). d In the absence (control) or presence of 5 μM BBR, ~50 islets from male C57BL/6 J mice were perfused with a low (2.8 mM) glucose concentration for 10 min followed by a high (16.7 mM) glucose concentration for 30 min. The amount of insulin secreted was normalized to the total insulin content. First phase (0–5 min), second phase and total insulin secretion were calculated as the area under the curve (AUC). n = 4. P = 0.042 for first phase, P = 0.036 for total insulin secretion. Statistical significance was assessed using the Mann–Whitney U-test (two-sided). e Approximately 50 islets were perfused with a low (2.8 mM) glucose concentration for 10 min and then with a high (16.7 mM) glucose concentration for 120 min. Afterwards, during the continuous perfusion of 16.7 mM glucose, the islets were treated with 5 μM BBR or vehicle (control) for 20 min followed by 30 mM KCl, which served as the internal control for islet viability, for 30 min. The amount of insulin secreted was normalized to the total insulin content. The dotted box represents insulin secretion from islets stimulated with 5 μM BBR or vehicle under high (16.7 mM)-glucose conditions. n = 4. P = 0.029. Statistical significance was assessed using the Mann–Whitney U-test (two-sided). f, g Mice islets were treated with or without 5 μM BBR or BBR plus 1 μM glibenclamide (f) /100 μM verapamil (g) in the presence of 25 mM glucose for 30 min. Insulin secretion was normalized to that of the control group. n = 6. P = 0.042 for glucose, P = 0.015 for glucose plus glibenclamide in f. P = 0.025 for glucose, P = 0.171 for glucose plus verapamil in g Statistical significance was assessed using the Mann–Whitney U-test (two-sided). The values are presented as means ± s.e.m. *P < 0.05.