title: The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro.
abstract: Diet-derived short chain fatty acids (SCFAs) improve glucose homeostasis in vivo, but the role of individual SCFAs and their mechanisms of action have not been defined. This study evaluated the effects of increasing colonic delivery of the SCFA propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro.
  
  
  
  For 24 weeks human subjects ingested an inulin-propionate ester that delivers propionate to the colon. Acute insulin, GLP-1 and non-esterified fatty acid (NEFA) levels were quantified pre- and post-supplementation in response to a mixed meal test. Expression of the SCFA receptor FFAR2 in human islets was determined by western blotting and immunohistochemistry. Dynamic insulin secretion from perifused human islets was quantified by radioimmunoassay and islet apoptosis was determined by quantification of caspase 3/7 activities.
  
  
  
  Colonic propionate delivery in vivo was associated with improved β-cell function with increased insulin secretion that was independent of changes in GLP-1 levels. Human islet β-cells expressed FFAR2 and propionate potentiated dynamic glucose-stimulated insulin secretion in vitro, an effect that was dependent on signalling via protein kinase C. Propionate also protected human islets from apoptosis induced by the NEFA sodium palmitate and inflammatory cytokines.
  
  
  
  Our results indicate that propionate has beneficial effects on β-cell function in vivo, and in vitro analyses demonstrated that it has direct effects to potentiate glucose-stimulated insulin release and maintain β-cell mass through inhibition of apoptosis. These observations support ingestion of propiogenic dietary fibres to maintain healthy glucose homeostasis.
authors.affiliation: Division of Diabetes and Nutritional Sciences, Diabetes Research Group, King's College London, London, UK.
authors.forename: Attilio
authors.initials: A
authors.lastname: Pingitore
authors.affiliation: Faculty of Medicine, Nutrition and Dietetic Research Group, Imperial College London, London, UK.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Chambers
authors.affiliation: Division of Diabetes and Nutritional Sciences, Diabetes Research Group, King's College London, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hill
authors.affiliation: Division of Diabetes and Nutritional Sciences, Diabetes Research Group, King's College London, London, UK.
authors.forename: Inmaculada Ruz
authors.initials: IR
authors.lastname: Maldonado
authors.affiliation: Division of Diabetes and Nutritional Sciences, Diabetes Research Group, King's College London, London, UK.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Division of Diabetes and Nutritional Sciences, Diabetes Research Group, King's College London, London, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Bewick
authors.affiliation: Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Morrison
authors.affiliation: Stable Isotope Biochemistry Laboratory, Scottish Universities Environmental Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Preston
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Gareth A
authors.initials: GA
authors.lastname: Wallis
authors.affiliation: School of Science, University of the West of Scotland, Hamilton, UK.
authors.forename: Catriona
authors.initials: C
authors.lastname: Tedford
authors.affiliation: Department of General Surgery, Rio Carrión Hospital, University Hospital Complex of Palencia, Palencia, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Castañera González
authors.affiliation: Division of Diabetes and Nutritional Sciences, Diabetes Research Group, King's College London, London, UK.
authors.forename: Guo C
authors.initials: GC
authors.lastname: Huang
authors.affiliation: Division of Diabetes and Nutritional Sciences, Diabetes Research Group, King's College London, London, UK.
authors.forename: Pratik
authors.initials: P
authors.lastname: Choudhary
authors.affiliation: Faculty of Medicine, Nutrition and Dietetic Research Group, Imperial College London, London, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Frost
authors.affiliation: Division of Diabetes and Nutritional Sciences, Diabetes Research Group, King's College London, London, UK.
authors.forename: Shanta J
authors.initials: SJ
authors.lastname: Persaud
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053179:Caspase 7 / Q000187:drug effects / Q000378:metabolism; D003106:Colon; D004041:Dietary Fats; D004952:Esters / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005232:Fatty Acids, Volatile; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007444:Inulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011422:Propionates / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled
chemical_list: D053148:Caspase 3; D053179:Caspase 7; D004041:Dietary Fats; D004952:Esters; D005230:Fatty Acids, Nonesterified; D005232:Fatty Acids, Volatile; D052216:Glucagon-Like Peptide 1; D007328:Insulin; D007444:Inulin; D011422:Propionates; D011956:Receptors, Cell Surface; C473103:FFAR2 protein, human; D043562:Receptors, G-Protein-Coupled; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C029658:propionic acid
keywords: beta cell; dietary intervention; insulin secretion; islets; short chain fatty acids; type 2 diabetes