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Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production
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- Lee, Ying Shiuan (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- De Vadder, Filipe (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Tremaroli, Valentina, 1978 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
- show more...
- Mithieux, G. (author)
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- (creator_code:org_t)
- Elsevier BV, 2016
- 2016
- English.
- In: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 5:4, s. 263-270
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- Insulin-like peptide 5 (INSL5)
- Gut microbiota
- Liver
- Colon
- glucagon-like peptide-1
- relaxin family peptides
- perfused-rat-liver
- growth factor-i
- neuroendocrine tumors
- energy-metabolism
- muscarinic
- nerves
- portal-vein
- mice
- homeostasis
- Endocrinology & Metabolism
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- ref (subject category)
- art (subject category)
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