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GIP(6-30)Cex-K⁴⁰[Pal] has been characterised as a fatty-acid-derived gastric inhibitory polypeptide (GIP) inhibitor that can induce pancreatic beta cell rest by diminishing the incretin effect. We investigated its therapeutic efficacy with and without the glucagon-like peptide-1 (GLP-1) beta cell cytotropic agent liraglutide.

The therapeutic efficacy of GIP(6-30)Cex-K⁴⁰[Pal] alone, and in combination with liraglutide, was determined in C57BL/KsJ db/db mice using a sequential 12 h administration schedule.

GIP(6-30)Cex-K⁴⁰[Pal] was devoid of cAMP-generating or insulin-secretory activity, and inhibited GIP-induced cAMP production and insulin secretion. GIP(6-30)Cex-K⁴⁰[Pal] also inhibited GIP-induced glucose-lowering and insulin-releasing actions in mice. Dose- and time-dependent …