Cyclo(His-Pro) augments the insulin response to oral glucose in rats

Cyclo(His-Pro) (CHP) is a gut-brain peptide found in rat and man. Since plasma levels of CHP are altered by oral glucose ingestion, we wondered whether exogenous CHP might alter the insulin response to oral glucose ingestion. To this end, rats were given 3g/kg oral glucose load with either saline or increasing doses of CHP and plasma levels of insulin, C-peptide and glucose were measured. We found mean insulin but not C-peptide excursions and area under the insulin but not C-peptide response curves (AUC) were significantly higher in the CHP groups than controls despite similar glucose responses. In summary, these data show that in rats receiving oral glucose, CHP causes higher insulin excursions without any change in C-peptide suggesting that CHP may decrease hepatic insulin clearance.