PHI structural requirements for potentiation of glucose-induced insulin release.
Immunoreactive PHI was detected in rat pancreas. The potentiating effect of 10(-9) M PHI upon insulin release from the isolated perfused rat pancreas was significant and most consistent when 250 mg% glucose was present in the perfusion medium. PHI(1-15) retained a substantial potentiating effect on insulin release, while PHI(14-27) was essentially inactive. Replacement of amino-terminal decapeptide portion of the PHI molecule with the corresponding part of VIP resulted in a drastic decrease of the potentiating effect of PHI on insulin release. 10(-8) M PHI(14-27) substantially diminished the potentiation by 10(-9) M PHI while PHI(1-15) was without an inhibitory effect. The present results indicate that the PHI active site for potentiation of glucose-induced insulin release resides in the amino-terminal segment of the molecule but requires the carboxyl terminal segment primarily for binding to exhibit full biological activity.
D000818:Animals; D001665:Binding Sites; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010451:Peptide PHI; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D007328:Insulin; D010446:Peptide Fragments; D010451:Peptide PHI; D010455:Peptides; D005947:Glucose