Activation of gut calcium‐sensing receptor by peptide agonists promotes glucose tolerance in rats

Abstract

PurposeCalcium‐sensing receptor (CaSR) is widely expressed in various tissues including gastrointestinal tract. However, the role of gut CaSR in digestion/absorption of macronutrients is yet not known. In the present study, we examined whether single oral administration of CaSR agonist peptides affects glycemic response in rats, and also investigated the mechanism by which CaSR agonists modulate the glycemic response.MethodsGlucose tolerance tests were performed under oral or duodenal administration of various CaSR agonist peptides {γGlu‐Cys (γEC), protamine, and poly‐lysine} in conscious rats. Gastric emptying rate was measure by using phenol red method.ResultsOral and duodenal administration of CaSR agonists (γEC, protamine, and poly‐lysine) attenuated the glycemic response under oral glucose tolerance test. Gastric emptying rate was decreased by oral administration of these CaSR agonists. Glucose‐lowering effect of the agonists was partially cancelled by luminal pretreatment with a CaSR inhibitor. In addition, intraperitoneal treatment with 5‐HT3 receptor antagonist partially reversed the glucose‐lowering effect of the agonists.These results demonstrate the activation of gut CaSR by peptide agonists attenuates glycemic response. Involvement of 5‐HT3 receptor and delayed gastric emptying are suggested in the glucose‐lowering effect of these CaSR agonists.