The effects of cerulenin, an inhibitor of protein acylation, on the two phases of glucose-stimulated insulin secretion.
The potential role of protein acylation in the control of biphasic insulin secretion has been studied in isolated rat pancreatic islets. The protein acylation inhibitor cerulenin inhibited both phases of glucose-stimulated insulin secretion. However, it did not affect the secretory response to a depolarizing concentration of KCl in either the absence or presence of diazoxide. Therefore, cerulenin has no deleterious effect on the L-type Ca(2+) channels or subsequent events in Ca(2+) stimulus-secretion coupling. Advantage was taken of this to study the effect of cerulenin on the K(ATP) channel-independent pathway of glucose signaling. In the presence of KCl and diazoxide, cerulenin powerfully inhibited the augmentation of insulin release by glucose and palmitate. Similar inhibition of the augmentation of release by glucose and palmitate was seen under Ca(2+)-free conditions in the presence of 12-O-tetradecanoylphorbol-13-acetate and forskolin. As neither glucose oxidation nor the effect of glucose to inhibit fatty acid oxidation is affected by cerulenin, these data suggest that protein acylation is involved in the K(ATP) channel-independent pathway of glucose signaling.
Straub
Susanne G
SG
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Yajima
Hiroki
H
Komatsu
Mitsuhisa
M
Aizawa
Toru
T
Sharp
Geoffrey W G
GW
D000215:Acylation / Q000187:drug effects; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002569:Cerulenin / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D000935:Antifungal Agents; D007328:Insulin; D014665:Vasodilator Agents; D002569:Cerulenin; D011189:Potassium Chloride; D005947:Glucose; D003981:Diazoxide; D002118:Calcium