Calcium-Sensing Receptor Regulation of Gastrointestinal Hormone Secretion

Area of Science:

• Gastroenterology and Endocrinology
• Nutritional Science
• Molecular Biology

Background:

• Dietary nutrients interact with gastrointestinal chemoreceptors, influencing gut hormone secretion, digestion, absorption, energy intake, and postprandial glycemia.
• The calcium-sensing receptor (CaSR), initially identified for sensing extracellular calcium (Ca2+), also binds L-amino acids (AAs), including L-tryptophan (L-Trp) and L-phenylalanine (L-Phe).
• CaSR is expressed in enteroendocrine cells of the stomach and small intestine, mediating gut hormone release in response to AAs and Ca2+.

Purpose of the Study:

• To review preclinical and clinical evidence on the role of CaSR activators in modulating gut hormones.
• To explore the impact of CaSR activation on energy intake and postprandial glycemia.
• To discuss the therapeutic potential of CaSR activators for metabolic disorders like obesity and type 2 diabetes.

Main Methods:

• Review of preclinical studies investigating CaSR function in gut hormone secretion.
• Analysis of clinical trials involving intraluminal administration of CaSR activators (L-Trp, L-Phe, Ca2+).
• Examination of data on plasma gut hormone levels, energy intake, and postprandial glucose responses.

Main Results:

• Intraluminal administration of L-Trp or L-Phe in humans increases gut hormone levels, reducing energy intake and postprandial glucose response.
• Extracellular Ca2+ enhances the effects of L-Trp on gut hormone secretion (including CCK, GLP-1, PYY) and energy intake reduction.
• CaSR activators, including Ca2+, L-Trp, and L-Phe, stimulate gut hormones and lower both energy intake and postprandial glycemia.

Conclusions:

• CaSR activators represent a promising nutrient-based approach for managing obesity and type 2 diabetes.
• Targeting CaSR offers a novel therapeutic strategy for metabolic diseases.
• Further research into CaSR pathways could lead to innovative dietary interventions.