Islet effects of cholecystokinin and exploitation in diabetes

Within pancreatic islets, cholecystokinin (CCK) receptor activation potentiates beta-cell function and survival, and these benefits could be exploited for diabetes. Unfortunately, native CCK has a short biological half-life due to rapid enzymatic degradation in the circulation, thereby limiting potential therapeutic usefulness. However, enzyme-resistant longer-acting CCK analogs have been developed that retain bioactivity and display marked benefits on islet function and diabetes. Also, when CCK peptides are administered in combination with other islet modulators and/or glucoregulatory agents, including the incretin hormones, additive or even synergistic metabolic benefits are observed. This combined administration approach also permits reduced CCK dose requirements, thereby minimizing possible adverse off-target side effects. Optimizing such CCK coagonists, and augmenting positive pancreatic islets’ actions, could yield safe and efficacious treatment options for diabetes.