Comparison of the independent and combined metabolic effects of subchronic modulation of CCK and GIP receptor action in obesity-related diabetes

OBJECTIVE: Compromise of gastric inhibitory polypeptide (GIP) receptor action and activation of cholecystokinin (CCK) receptors represent mechanistically different approaches to the possible treatment of obesity-related diabetes. In the present study, we have compared the individual and combined effects of (Pro(3))GIP[mPEG] and (pGlu-Gln)-CCK-8 as an enzymatically stable GIP receptor antagonist and CCK receptor agonist molecule, respectively. RESULTS: Twice-daily injections of (pGlu-Gln)-CCK-8 alone and in combination with (Pro(3))GIP[mPEG] in high-fat-fed mice for 34 days significantly decreased the energy intake throughout the entire study (P