title: Activation of the gut calcium-sensing receptor by peptide agonists reduces rapid elevation of plasma glucose in response to oral glucose load in rats.
abstract: The calcium-sensing receptor (CaSR) is expressed in various tissues, including the gastrointestinal tract. To investigate the role of gut CaSR on glycemic control, we examined whether single oral administration of CaSR agonist peptides affected the glycemic response in rats. Glucose tolerance tests were performed under oral or duodenal administration of various CaSR agonist peptides (γGlu-Cys, protamine, and poly-d-lysine hydrobromide) in conscious rats. Involvement of CaSR was determined by using a CaSR antagonist. Signaling pathways underlying CaSR agonist-modified glycemia were investigated using gut hormone receptor antagonists. The gastric emptying rate after the administration of CaSR agonist peptides was measured by the phenol red recovery method. Oral and duodenal administration of CaSR agonist peptides attenuated glycemic responses under the oral glucose tolerance test, but the administration of casein did not. The promotive effect on glucose tolerance was weakened by luminal pretreatment with a CaSR antagonist. Treatment with a 5-HT3 receptor antagonist partially diminished the glucose-lowering effect of peptides. Furthermore, the gastric emptying rate was decreased by duodenal administration of CaSR agonist peptides. These results demonstrate that activation of the gut CaSR by peptide agonists promotes glucose tolerance in conscious rats. 5-HT3 receptor and the delayed gastric emptying rate appear to be involved in the glucose-lowering effect of CaSR agonist peptides. Thus, activation of gut CaSR by dietary peptides reduces glycemic responses so that gut CaSR may be a potential target for the improvement of postprandial glycemia.
authors.affiliation: Graduate School of Agriculture, Hokkaido University, Sapporo, Japan;
authors.forename: Maya
authors.initials: M
authors.lastname: Muramatsu
authors.affiliation: Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan; hira@chem.agr.hokudai.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Hira
authors.affiliation: Faculty of Agriculture, Hokkaido University, Sapporo, Japan; and.
authors.forename: Arimi
authors.initials: A
authors.lastname: Mitsunaga
authors.affiliation: Graduate School of Agriculture, Hokkaido University, Sapporo, Japan;
authors.forename: Eri
authors.initials: E
authors.lastname: Sato
authors.affiliation: Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan;
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Faculty of Agriculture, Hokkaido University, Sapporo, Japan; and.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kitahara
authors.affiliation: Faculty of Agriculture, Hokkaido University, Sapporo, Japan; and.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Eto
authors.affiliation: Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hara
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D008297:Male; D019518:Postprandial Period; D011479:Protamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000819:agonists* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011479:Protamines; D044169:Receptors, Calcium-Sensing; D044406:Receptors, Serotonin, 5-HT3; D052216:Glucagon-Like Peptide 1; D005947:Glucose
keywords: dietary peptides; gastric emptying; glycemic control