Insulin-like activities and insulin-potentiating actions of a modified insulin B21-26 fragment: beta-Ala-Arg-Gly-Phe-Phe-Tyr-NH2.

Abstract

A modified sequence of insulin B21-26, beta-Ala-Arg-Gly-Phe-Phe-Tyr-NH2 (DP-432), was synthesized and tested for its biological activities. The hexapeptide, ip injected to mice, stimulated [U-14C]-glucose incorporation into diaphragm glycogen and adipose tissue total lipid. Neither plasma glucose nor FFA (free fatty acid) was reduced by the injection. However, when injected with epinephrine, the peptide prevented a rise of plasma FFA but not that of plasma glucose due to epinephrine. In vitro, the peptide stimulated glucose oxidation and inhibited epinephrine- or isoproterenol-stimulated lipolysis of mouse adipose tissue. Furthermore, when added along with insulin to incubation media, the peptide exaggerated the effects of insulin on both glucose oxidation and isoproterenol-stimulated lipolysis. The hexapeptide thus seems to have an insulin-potentiating action as well as insulin like activities on peripheral tissue.