title: RANTES (CCL5) reduces glucose-dependent secretion of glucagon-like peptides 1 and 2 and impairs glucose-induced insulin secretion in mice.
abstract: Type 2 diabetes is associated with elevated circulating levels of the chemokine RANTES and with decreased plasma levels of the incretin hormone glucagon-like peptide 1 (GLP-1). GLP-1 is a peptide secreted from intestinal L-cells upon nutrient ingestion. It enhances insulin secretion from pancreatic β-cells and protects from β-cell loss but also promotes satiety and weight loss. In search of chemokines that may reduce GLP-1 secretion we identified RANTES and show that it reduces glucose-stimulated GLP-1 secretion in the human enteroendocrine cell line NCI-H716, blocked by the antagonist Met-RANTES, and in vivo in mice. RANTES exposure to mouse intestinal tissues lowers transport function of the intestinal glucose transporter SGLT1, and administration in mice reduces plasma GLP-1 and GLP-2 levels after an oral glucose load and thereby impairs insulin secretion. These data show that RANTES is involved in altered secretion of glucagon-like peptide hormones most probably acting through SGLT1, and our study identifies the RANTES-receptor CCR1 as a potential target in diabetes therapy.
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Nutritional Medicine, Technische Universität München, Freising, Germany; ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany; and.
authors.forename: Ramona
authors.initials: R
authors.lastname: Pais
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany; and.
authors.forename: Tamara
authors.initials: T
authors.lastname: Zietek
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Nutritional Medicine, Technische Universität München, Freising, Germany; Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany; and.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Nutritional Medicine, Technische Universität München, Freising, Germany; Klinikum rechts der Isar, Technische Universität München, Munich, Germany skurk@tum.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Skurk
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002460:Cell Line; D018946:Chemokine CCL5 / Q000008:administration & dosage / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D053767:Glucagon-Like Peptide 2 / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D054389:Receptors, CCR1 / Q000235:genetics / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D001786:Blood Glucose; C483024:CCL5 protein, human; C515300:CCR1 protein, human; D018946:Chemokine CCL5; D053767:Glucagon-Like Peptide 2; D007328:Insulin; D054389:Receptors, CCR1; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP
keywords: RANTES; cAMP; glucagon-like peptide-1; sodium/glucose transporter-1