Molecular characterization of the glucose-sensing mechanism in the clonal insulin-secreting BRIN-BD11 cell line.
BRIN-BD11 cells represent a novel insulin-secreting cell line generated by electrofusion. Molecular characterization of these cells demonstrated the presence of mRNA and protein for the two key elements of the beta cell glucose-sensing system, GLUT2 and glucokinase. While levels of GLUT2 expression and 3-O-methyl-D-glucose equilibration were similar for both the BRIN-BD11 cell line and the parental control RINm5F cells, glucokinase expression was substantially higher in BRIN-BD11 cells. Expression of the two-component KATP channel complex, KIR6.2 and SUR1, was similar in both cells. However, while control RINm5F cells were completely unresponsive to glucose, BRIN-BD11 cells responded to physiological millimolar concentrations of this hexose sugar. These studies strongly suggest that the glucose-sensing ability of insulin-secreting cells is largely dictated by the level of glucokinase, as opposed to GLUT2, expression. Thus, BRIN-BD11 cells expressing the key attributes of the normal beta cell provide an interesting model for elucidation of regulatory principles of beta cell function.
McClenaghan
N H
NH
Institute of Clinical Biochemistry, Hannover Medical School, Germany.
Elsner
M
M
Tiedge
M
M
Lenzen
S
S
D019325:3-O-Methylglucose / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002459:Cell Fusion; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D005941:Glucokinase / Q000032:analysis / Q000235:genetics; D005947:Glucose / Q000494:pharmacology*; D051273:Glucose Transporter Type 2; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics; D015221:Potassium Channels / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D015221:Potassium Channels; D012333:RNA, Messenger; D019325:3-O-Methylglucose; D005941:Glucokinase; D005947:Glucose