Transcription factor AP-2beta inhibits glucose-induced insulin secretion in cultured insulin-secreting cell-line.
OBJECTIVE
We previously identified the transcription factor activating enhancer-binding protein-2beta (AP-2beta) gene as a new candidate for conferring susceptibility to type 2 diabetes. To ascertain the possible involvement of AP-2beta in the pathogenesis of type 2 diabetes we examined the effects of AP-2beta on glucose-induced insulin secretion.


METHODS
We measured the insulin secretion stimulated by glucose, tolbutamide, or KCl in the HIT-T15 cells infected with adenovirus vectors encoding AP-2beta or LacZ (control).


RESULTS
We identified clear expression of AP-2beta in isolated rat pancreatic islets and in HIT-T15 cells. Glucose-induced increase in insulin secretion was significantly inhibited in AP-2beta-overexpressing cells (LacZ, 5.0+/-0.8 ng h(-1)mg(-1) protein; AP-2beta, 1.7+/-0.2 ng h(-1)mg(-1) protein; P=0.0015), whereas insulin expression was the same in both types of cells. Tolbutamide-induced insulin secretion was also suppressed in the AP-2beta-overexpressing cells, but KCl-induced insulin secretion was not affected by AP-2beta overexpression. In addition, Kir6.2 and glucokinase expression was significantly decreased in the AP-2beta-overexpressing cells.


CONCLUSIONS
We identified for the first time that AP-2beta expressed and functioned in insulin-secreting cell-line HIT-T15. These results suggest that AP-2beta contributes to susceptibility to type 2 diabetes by inhibiting glucose-induced insulin secretion in pancreatic beta cells.
Tsukada
Shuichi
S
Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Kobayashi
Masa-Aki
MA
Omori
Shintaro
S
Unoki
Hiroyuki
H
Maeda
Shiro
S
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014044:Tolbutamide / Q000494:pharmacology; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000494:pharmacology*
D017931:DNA Primers; D007328:Insulin; D050656:Transcription Factor AP-2; D014044:Tolbutamide; D005947:Glucose