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Mol Metab. 2016 Jan 25;5(4):263-270. doi: 10.1016/j.molmet.2016.01.007. eCollection 2016 Apr.

Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production.

Author information

1
The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
2
The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Institut National de la Santé et de la Recherche Médicale, U855, Lyon 69372, France; Université de Lyon, Lyon 69008, France; Université Lyon 1, Villeurbanne 69622, France.
3
Institut National de la Santé et de la Recherche Médicale, U855, Lyon 69372, France; Université de Lyon, Lyon 69008, France; Université Lyon 1, Villeurbanne 69622, France.
4
The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: Fredrik.Backhed@wlab.gu.se.

Abstract

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.

KEYWORDS:

Colon; Gut microbiota; Insulin-like peptide 5 (INSL5); Liver

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