Objective       To determine the role of mibefradil on the insulin secretion of the islet cells under high glucose environment.       Methods       Rat insulinoma INS-1 cells were cultured with RPMI 1640 including 10% FBS under 37℃ and 5% CO

2

in vitro. The cells were randomly divided into 4 groups

that is

control group (11.1 mmol/L glucose)

high glucose gr

oup (33.3 mmol/L glucose)

drug group (11.1 mmol/L glucose+1 μmol/L mibefradil

1 μmol/L NNC 55-0396

10 μmol/L nicardipine)

and high glucose+drug group (33.3 mmol/L glucose+1 μmol/L mibefradil

1 μmol/L NNC 55-0396

10 μmol/L nicardipine). The cells in each group had been treated with different concentrations of glucose for 48 h

and then incubated with corresponding drugs for another 24 h. The insulin secretion of INS-1 cells in the cell supernatant was measured by radioimmunoassay. The expression of T-type calcium channel subunits cav3.1 and cav3.2 at mRNA and protein levels was detected by RT-PCR and Western blotting respectively.       Results       Compared with the control group

high glucose inducement resulted in obviously increased insulin release in the cell supernatant (P0.05)

and markedly increased expression levels of cav3.1 and cav3.2 (P0.05). In addition

there was no significant difference in the insulin release and the expression levels of the subunits between the control group and the drug group (P0.05). Compared with the high glucose group

high glucose + drug treatment decreased the insulin release in the cell supernatant. Among them

high glucose+mibefradil showed stronger inhibition on insulin secretion (P0.05) and the expression of the subunits at mRNA and protein levels (P0.05).       Conclusion       Mibefradil may inhibits the insulin release of INS-1 cells under high glucose circumstance through down-regulating the expression levels of T-type calcium channels subunits cav3.1 and cav3.2.