| First Author | Pais R | Year | 2014 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 307 |
| Issue | 3 | Pages | G330-7 |
| PubMed ID | 24875103 | Mgi Jnum | J:221714 |
| Mgi Id | MGI:5641407 | Doi | 10.1152/ajpgi.00329.2013 |
| Citation | Pais R, et al. (2014) RANTES (CCL5) reduces glucose-dependent secretion of glucagon-like peptides 1 and 2 and impairs glucose-induced insulin secretion in mice. Am J Physiol Gastrointest Liver Physiol 307(3):G330-7 |
| abstractText | 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 beta-cells and protects from beta-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. |
