The protective effect of berberine on β-cell lipoapoptosis.
OBJECTIVE
To evaluate the protective effect of berberine on β-cell lipoapoptosis induced by palmitate and to explore the possible underlying mechanisms.


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.


CONCLUSIONS
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.
Gao
N
N
Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, GuoXue Lane 37, Chengdu, Sichuan, 610041 RP China.
Zhao
T-Y
TY
Li
X-J
XJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology*
D007328:Insulin; D047495:PPAR gamma; D010168:Palmitates; D001599:Berberine