{
  "abstract": "Objective Enterosynes are bioactive molecules that control gut motility via the enteric nervous system. The large majority of these molecules target nitrergic enteric neurons, stimulating intestinal nitric oxide (NO) release. NO is a neurotransmitter that inhibits intestinal smooth muscle cells, thereby improving glucose homeostasis through gut–brain axis-mediated systemic effects. In this work, we investigated the effect of catestatin, a peptide known to inhibit acetylcholine signalling, a major stimulatory neurotransmitter of gut motility that also plays a key role in glycaemic control.Design We assessed the effects of catestatin on gut motility, intestinal NO release, glucose homeostasis and messenger RNA expression of metabolic markers in different tissues (intestine, brain, liver, adipose tissue and muscle) in male mice fed a high-fat diet. The effects of catestatin were measured after 1-week and 6-week oral administration.Results We demonstrate that acute or 1-week chronic treatments of catestatin decrease duodenal hypermotility in diabetic mice. This effect is associated with improved glucose tolerance and reduced glucose-stimulated insulin secretion. This enhanced blood glucose control in obese/diabetic mice under catestatin is accompanied by favourable transcriptomic changes in metabolic tissues. Long-term (6 weeks) oral treatment with catestatin in mice fed a high-fat diet decreases body weight gain and improves glucose tolerance. These effects are associated with a significant reduction of hepatic triglycerides in the liver.Conclusion We discovered that catestatin exerts an enterosyne-like effect on gut motility and glucose metabolism without stimulating intestinal NO. This result highlights a promising approach for improving hyperglycaemia in metabolic disorders.",
  "authors": [
    {
      "affiliations": [
        "Enterosys SAS, Labege, France"
      ],
      "name": "Anne Abot"
    },
    {
      "affiliations": [
        "Université de Toulouse, Toulouse, France",
        "INSERM Regional Delegation Occitanie Pyrénées, Toulouse, France",
        "NeuroMicrobiota lab, INSERM/UCLouvain, Toulouse, France"
      ],
      "name": "Céline El Samrout"
    },
    {
      "affiliations": [
        "Université de Toulouse, Toulouse, France",
        "INSERM Regional Delegation Occitanie Pyrénées, Toulouse, France",
        "NeuroMicrobiota lab, INSERM/UCLouvain, Toulouse, France",
        "Pathology Post Graduate Program, Fluminense Federal University (UFF), Rio de Janeiro, Brazil"
      ],
      "name": "Milena Barcza Stockler-Pinto"
    },
    {
      "affiliations": [
        "Université de Toulouse, Toulouse, France",
        "INSERM Regional Delegation Occitanie Pyrénées, Toulouse, France"
      ],
      "name": "Jean Monlong"
    },
    {
      "affiliations": [
        "Université de Toulouse, Toulouse, France",
        "INSERM Regional Delegation Occitanie Pyrénées, Toulouse, France"
      ],
      "name": "Sarah Djebali"
    },
    {
      "affiliations": [
        "Institute of Metabolic and Cardiovascular Diseases (I2MC), INSERM, Paris, France"
      ],
      "name": "Cédric Moro"
    },
    {
      "affiliations": [
        "NeuroMicrobiota lab, INSERM/UCLouvain, Toulouse, France",
        "Louvain Drug Research Institute (LDRI), Metabolism and Nutrition research group (MNUT), UCLouvain, Brussels, Belgium",
        "Walloon Excellence in LifeSciences and BIOtechnology (WELBIO) department, WELResearch Institute, Wavre, Belgium",
        "Institute of Experimental and Clinical Research (IREC), UCLouvain, Brussels, Belgium",
        "Section of Biomolecular Medicine, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK"
      ],
      "name": "Patrice D Cani"
    },
    {
      "affiliations": [
        "Université de Toulouse, Toulouse, France",
        "INSERM Regional Delegation Occitanie Pyrénées, Toulouse, France",
        "NeuroMicrobiota lab, INSERM/UCLouvain, Toulouse, France"
      ],
      "name": "Claude Knauf"
    }
  ],
  "title": "Catestatin decreases duodenal hypermotility to improve glucose homeostasis in diabetic male mice",
  "uid": "836125d4-7a96-5607-9b17-190bc509b8ff"
}