CCk8 Enhances Anti‐diabetic Efficacy of GLP1

Abstract

The objective of the study is to investigate potential synergistic or additive effects of combining GLP1 with CCK8 in diet induced obese (DIO) mice. Glucagon‐like peptide‐1 (GLP1) is a peptide hormone secreted by the intestinal L cells in response to food ingestion. It augments glucose‐mediated insulin secretion, inhibits glucagon secretion, reduces appetite and food intake, and delays gastric emptying. Another gastrointestinal peptide released upon food ingestion is cholecystokinin (CCK). CCK is secreted from the duodenal I cells in response to fat and protein. CCK can stimulate pancreatic enzyme secretion, increase gall bladder contractions and delay gastric emptying. CCK also triggers a gut‐brain‐liver neuronal network to control glucose production. The major form of biologically active CCK is CCK‐8. When DIO mice were infused with low doses of a GLP1 analog or a CCK8 analog for two weeks, no effects on food intake or body weight were observed. However, the group received both peptides (GLP1+CCK8) showed significant reductions in food intake and body weight. At the completion of two‐week treatments, both GLP1‐ and CCK8‐treated groups decreased glucose excursion in response to an oral glucose challenge. The GLP1+CCK8 group demonstrated additive effects on glucose lowering. In conclusion, combination of GLP1 with CCK8 has the potential to be a more efficacious therapy for type II diabetes.