Modulation of insulin secretion by diazepam binding inhibitor and its processing products.
The effect of purified rat brain diazepam binding inhibitor (DBI) and that of synthetic DBI fragments DBI33-50 [octadecaneuropeptide (ODN)], DBI17-50 [triakontatetraneuropeptide (TTN)], DBI42-50 and DBI53-62 were studied on glucose-induced secretion of insulin from isolated rat pancreatic islets in both static incubation and perifusion experiments. DBI and ODN did not affect the secretion of insulin in the presence of 2.8 mM glucose (basal condition) but reduced the release of insulin induced by 16.7 mM glucose. The effects of DBI and ODN were significant at concentrations as small as 1-10 nM. In contrast, 100 nM TTN, DBI42-50 (which corresponds to the COOH-terminal region of ODN) and DBI53-62 (which corresponds to a region of DBI that is conserved among species), were without effect on both basal and 16.7 mM glucose-stimulated insulin secretion. DBI has previously been localized to the delta cells of islets of Langerhans (Ostenson, Ahren, Karlsson, Sandberg and Efendic, 1990) and the presence of DBI- and ODN-like immunoreactivity in isolated rat pancreatic islets has now been demonstrated. These results suggest that DBI and some of its processing products (ODN) may modulate glucose-stimulated secretion of insulin through a paracrine mechanism.
Borboni
P
P
Department of Internal Medicine-Endocrinology, II University of Rome Tor Vergata, Italy.
Condorelli
L
L
De Stefanis
P
P
Sesti
G
G
Lauro
R
R
D000818:Animals; D026261:Diazepam Binding Inhibitor; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology; D013329:Structure-Activity Relationship
D026261:Diazepam Binding Inhibitor; D007328:Insulin; D009479:Neuropeptides; D010446:Peptide Fragments; D011963:Receptors, GABA-A; D005947:Glucose