An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice.

ABSTRACT:

Aims/hypothesis

Glucose-dependent insulinotropic polypeptide (GIP) and xenin, regulatory gut hormones secreted from enteroendocrine K cells, exert important effects on metabolism. In addition, xenin potentiates the biological actions of GIP. The present study assessed the actions and therapeutic utility of a (DAla²)GIP/xenin-8-Gln hybrid peptide, in comparison with the parent peptides (DAla²)GIP and xenin-8-Gln.

Methods

Following confirmation of enzymatic stability, insulin secretory activity of (DAla²)GIP/xenin-8-Gln was assessed in BRIN-BD11 beta cells. Acute and persistent glucose-lowering and insulin-releasing effects were then examined in vivo. Finally, the metabolic benefits of twice daily injection of (DAla²)GIP/xenin-8-Gln

SUBMITTER: Hasib A 

PROVIDER: S-EPMC6518372 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature