Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production
| Autor: | Fredrik Bäckhed, Valentina Tremaroli, Anita Wichmann, Filipe De Vadder, Gilles Mithieux, Ying Shiuan Lee |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
lcsh:Internal medicine Hepatic glucose Colon 030209 endocrinology & metabolism Peptide Gut microbiota Gut flora 03 medical and health sciences 0302 clinical medicine lcsh:RC31-1245 Molecular Biology Gene Energy deficiency Insulin-like peptide 5 (INSL5) 2. Zero hunger chemistry.chemical_classification biology Cell Biology biology.organism_classification Cell biology 030104 developmental biology Liver chemistry Immunology Original Article Function (biology) Relaxin/insulin-like family peptide receptor 2 Hormone |
| Zdroj: | Molecular Metabolism Molecular Metabolism, Vol 5, Iss 4, Pp 263-270 (2016) |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2016.01.007 |
| Popis: | Objective Insulin-like peptide 5 (INSL5) is a recently identified gut hormone that is produced predominantly by L-cells in the colon, but its function is unclear. We have previously shown that colonic expression of the gene for the L-cell hormone GLP-1 is high in mice that lack a microbiota and thus have energy-deprived colonocytes. Our aim was to investigate if energy deficiency also affected colonic Insl5 expression and to identify a potential role of INSL5. Methods We analyzed colonic Insl5 expression in germ-free (GF), conventionally raised (CONV-R), conventionalized (CONV-D) and antibiotic-treated mice, and also assessed the effect of dietary changes on colonic Insl5 expression. In addition, we characterized the metabolic phenotype of Insl5−/− mice. Results We showed that colonic Insl5 expression was higher in GF and antibiotic-treated mice than in CONV-R mice, whereas Insl5 expression in the brain was higher in CONV-R versus GF mice. We also observed that colonic Insl5 expression was suppressed by increasing the energy supply in GF mice by colonization or high-fat feeding. We did not observe any differences in food intake, gut transit or oral glucose tolerance between Insl5−/− and wild-type mice. However, we showed impaired intraperitoneal glucose tolerance in Insl5−/− mice. We also observed improved insulin tolerance and reduced hepatic glucose production in Insl5−/− mice. Conclusions We have shown that colonic Insl5 expression is regulated by the gut microbiota and energy availability. We propose that INSL5 is a hormone that could play a role in promoting hepatic glucose production during periods of energy deprivation. Highlights • INSL5 is a microbially regulated peptide hormone. • Colonic INSL5 expression is suppressed by increased energy availability. • INSL5 promotes hepatic glucose production. |
| Databáze: | OpenAIRE |
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