The protective effect of berberine on β-cell lipoapoptosis.

AIMS: To evaluate the protective effect of berberine on β-cell lipoapoptosis induced by palmitate and to explore the possible underlying mechanisms.
MATERIALS AND METHODS: HIT-T15 pancreatic β-cells were divided into the following treatment groups: untreated controls; 100 μM berberine; 0.5 mM palmitate; 0.5 mM palmitate + 0.1 μM berberine; 0.5 mM palmitate + 1 μM berberine; 0.5 mM palmitate + 10 μM berberine; and 0.5 mM palmitate + 100 μM berberine. After 48 h, cell apoptosis was assessed by flow cytometry and the Hoechst 33258 fluorescent assay. Basal and glucose-stimulated insulin levels in culture medium were measured by radioimmunoassay. Peroxisome proliferator- activated receptor-γ (PPAR-γ) mRNA and protein levels were determined by real-time PCR and immunocytochemistry, respectively.
RESULTS: Apoptosis was significantly increased upon treatment with palmitate as compared to the untreated controls (p<0.0001). In addition, glucose-stimulated insulin secretion (GSIS), PPAR-γ mRNA and protein expression were significantly reduced in response to palmitate (p<0.0001); however, palmitate-induced apoptosis and reduction in PPAR-γ expression were reversed in response to berberine in a dose-dependent manner (p<0.05). Furthermore, there was a non-significant increase in GSIS with increasing berberine dose.
CONCLUSION: Palmitate exerted lipotoxic effects on HIT-T15 cells, inducing apoptosis and reducing GSIS. Berberine reduced palmitate-induced lipoapoptosis and tended to increase GSIS in HIT-T15 cells, possibly through increased PPAR-γ expression.