l-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents
Autor: | Murphy, KG, Spreckley, E, Norton, M, Alamshah, Kinsey-Jones, J, Amin, A, Ramgulam, A, Cao, Y, Johnson, R, Saleh, K, Jomard, A, Amarsi, R, Moolla, A, Akalestou, E, Malik, Z, Gonzalez Abuin, Sargent, P, Gray, G, Bloom, S |
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Přispěvatelé: | Medical Research Council (MRC), Innovate UK |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Male
Appetite Regulation Phenylalanine digestive oral and skin physiology 11 Medical And Health Sciences Satiation Rats Receptors Gastrointestinal Hormone Gastrointestinal Hormones Mice Inbred C57BL Endocrinology & Metabolism Disease Models Animal Eating Mice Appetite Depressants Glucose Intolerance Animals Original Article Rats Wistar Energy Metabolism 13 Education Receptors Calcium-Sensing |
Zdroj: | International Journal of Obesity (2005) |
ISSN: | 1476-5497 0307-0565 |
Popis: | Objectives: High protein diets are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which high protein diets exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may play a role in appetite regulation and satiety. We investigated the effects of L-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. Methods: We investigated the effects of the aromatic amino acid and calcium sensing receptor (CaSR) agonist L-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo. We also examined the effect of oral L-Phe administration on glucose tolerance in rats. Results: Oral administration of L-Phe acutely reduced food intake in rats and mice, and chronically reduced food intake and body weight in diet-induced obese mice. Ileal L-Phe also reduced food intake in rats. L-Phe stimulated GLP-1 and PYY release, and reduced plasma ghrelin, and also stimulated insulin release and improved glucose tolerance in rats. Pharmacological blockade of the CaSR attenuated the anorectic effect of intra-ileal L-Phe in rats, and L-Phe-induced GLP-1 release from STC-1 and primary L cells was attenuated by CaSR blockade. Conclusions: L-Phe reduced food intake, stimulated GLP-1 and PYY release and reduced plasma ghrelin in rodents. Our data provides evidence that the anorectic effects of L-Phe are mediated via the CaSR, and suggest that L-Phe and the CaSR system in the gastrointestinal tract may have therapeutic utility in the treatment of obesity and diabetes. Further work is required to determine the physiological role of the CaSR in protein sensing in the gut, and the role of this system in humans. |
Databáze: | OpenAIRE |
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