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Activation of gut calcium‐sensing receptor by peptide agonists promotes glucose tolerance in rats
Author(s) -
Hira Tohru,
Muramatsu Maya,
Mitsunaga Arimi,
Sato Eri,
Nakajima Shingo,
Kitahara Yoshiro,
Eto Yuzuru,
Hara Hiroshi
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1158.2
Subject(s) - calcium sensing receptor , gastric emptying , medicine , agonist , endocrinology , chemistry , oral administration , receptor , pharmacology , calcium , calcium metabolism , stomach
Purpose Calcium‐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. Methods Glucose 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. Results Oral 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‐HT 3 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‐HT 3 receptor and delayed gastric emptying are suggested in the glucose‐lowering effect of these CaSR agonists.