Isolation and characterization of porcine diazepam-binding inhibitor, a polypeptide not only of cerebral occurrence but also common in intestinal tissues and with effects on regulation of insulin release.
The polypeptide DBI (diazepam-binding inhibitor) has been purified from the porcine upper intestine, where it is abundant. Porcine mature DBI is composed of 86 amino acid residues and has a blocked N-terminus. The primary structure, the first DBI structure determined at the protein level, differs from those indirectly deduced for human and rat DBI at 11 and 17 positions, respectively. In total, the three mammalian DBIs differ at 22 positions but have exactly identical C-terminal 11-residue segments, highly charged and ending with C-terminal isoleucine. The porcine DBI inhibits both the early and the late phase of glucose-induced insulin release from the isolated perfused rat pancreas. Thus, the results identify by direct analysis the presence of DBI at a non-cerebral localization (gut), establish a novel structural form (porcine) and demonstrate a novel bioactivity (on insulin release). These aspects are of special interest in relation to the conserved segments, including the one at the C-terminal end, which may constitute functionally important parts of the polypeptide. It is possible that DBI belongs to a new family of gut polypeptides which inhibit glucose-mediated insulin release by hormonal and/or neurocrine mechanisms.
Chen
Z W
ZW
Department of Biochemistry II, Karolinska Institutet, Stockholm, Sweden.
Agerberth
B
B
Gell
K
K
Andersson
M
M
Mutt
V
V
Ostenson
C G
CG
Efendić
S
S
Barros-Söderling
J
J
Persson
B
B
Jörnvall
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002540:Cerebral Cortex / Q000032:analysis*; D026261:Diazepam Binding Inhibitor; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007422:Intestines / Q000032:analysis*; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000302:isolation & purification* / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects; D010446:Peptide Fragments / Q000302:isolation & purification; D011487:Protein Conformation; D051381:Rats; D013552:Swine; D013997:Time Factors
D026261:Diazepam Binding Inhibitor; D007328:Insulin; D009479:Neuropeptides; D010446:Peptide Fragments; D005947:Glucose