PHI structural requirements for potentiation of glucose-induced insulin release

Abstract

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.