Glucose regulates acetyl-CoA carboxylase gene expression in a pancreatic beta-cell line (INS-1).
Acetyl-CoA carboxylase (ACC) catalyzes the production of malonyl-CoA which may act as a metabolic coupling factor in nutrient-induced insulin release. We have studied the long term regulation of ACC by nutrients using the cell line INS-1. Glucose, from 5 to 20 mM, elicited a 15-fold increase in ACC mRNA. The effect was detected after 4 h and reached a maximum by 24 h. ACC protein accumulation followed that of ACC mRNA, and glucose did not modify the half-life of the ACC transcript. Glucose caused a dose-dependent rise in the glucose 6-phosphate content of INS-1 cells. 2-Deoxyglucose, which is phosphorylated by glucokinase but is not further metabolized, induced ACC mRNA. The effect of glucose was blocked by the glucokinase inhibitors mannoheptulose and glucosamine and was not mimicked by the 3-O-methyl or 6-deoxy analogues of glucose, which are not phosphorylated. Activation of the Ca2+, cAMP, and C-kinase pathways with high K+, forskolin, and phorbol 12-myristate 13 acetate, respectively, caused insulin release but not ACC mRNA induction. Basal insulin release, at 5 mM glucose, correlated with the ACC protein content of INS-1 cells preincubated for 24 h at various glucose concentrations. In conclusion, glucose is a potent inducer of the ACC gene, and glucose 6-phosphate may mediate its effect. Different signaling systems mediate the action of glucose on insulin release and ACC gene expression. The data strengthen the view that ACC plays a pivotal role in nutrient-induced insulin release.
Brun
T
T
Division de Biochimie Clinique, University of Geneva, Switzerland.
Roche
E
E
Kim
K H
KH
Prentki
M
M
D000103:Acetyl-CoA Carboxylase / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003847:Deoxyglucose / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D005941:Glucokinase / Q000037:antagonists & inhibitors; D005944:Glucosamine / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D008356:Mannoheptulose / Q000494:pharmacology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction
D005958:Glucosephosphates; D007328:Insulin; D012333:RNA, Messenger; D019298:Glucose-6-Phosphate; D008356:Mannoheptulose; D003847:Deoxyglucose; D005941:Glucokinase; D000103:Acetyl-CoA Carboxylase; D005947:Glucose; D005944:Glucosamine