The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro

Attilio Pingitore, Edward S. Chambers, Thomas Hill, Inmaculada Ruz Maldonado, Bo Liu, Gavin Bewick, Douglas J. Morrison, Tom Preston, Gareth A. Wallis, Catriona Tedford, Ramón Castañera González, Guo Cai Huang, Pratik Choudhary, Gary Frost, Shanta J. Persaud

Research output: Contribution to journalArticle

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Abstract

Aims
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.

Materials and Methods
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.

Results
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.

Conclusions
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.
Original languageEnglish
Pages (from-to)257-265
Number of pages9
JournalDiabetes, Obesity and Metabolism
Volume19
Issue number2
Early online date20 Oct 2016
DOIs
Publication statusPublished - 28 Feb 2017

Fingerprint

Volatile Fatty Acids
Propionates
Insulin
Diet
Glucose
Glucagon-Like Peptide 1
Apoptosis
Homeostasis
Fatty Acids
Caspase 7
Inulin
Palmitic Acid
In Vitro Techniques
Dietary Fiber
Islets of Langerhans
Caspase 3
Protein Kinase C
Radioimmunoassay
Meals
Colon

Keywords

  • beta cell
  • dietary intervention
  • insulin secretion
  • islets
  • short chain fatty acids
  • type 2 diabetes

Cite this

Pingitore, Attilio ; Chambers, Edward S. ; Hill, Thomas ; Maldonado, Inmaculada Ruz ; Liu, Bo ; Bewick, Gavin ; Morrison, Douglas J. ; Preston, Tom ; Wallis, Gareth A. ; Tedford, Catriona ; Castañera González, Ramón ; Huang, Guo Cai ; Choudhary, Pratik ; Frost, Gary ; Persaud, Shanta J. / The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. In: Diabetes, Obesity and Metabolism. 2017 ; Vol. 19, No. 2. pp. 257-265.
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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 = "AimsDiet-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.Materials and MethodsFor 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.ResultsColonic 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.ConclusionsOur 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.",
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author = "Attilio Pingitore and Chambers, {Edward S.} and Thomas Hill and Maldonado, {Inmaculada Ruz} and Bo Liu and Gavin Bewick and Morrison, {Douglas J.} and Tom Preston and Wallis, {Gareth A.} and Catriona Tedford and {Casta{\~n}era Gonz{\'a}lez}, Ram{\'o}n and Huang, {Guo Cai} and Pratik Choudhary and Gary Frost and Persaud, {Shanta J.}",
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Pingitore, A, Chambers, ES, Hill, T, Maldonado, IR, Liu, B, Bewick, G, Morrison, DJ, Preston, T, Wallis, GA, Tedford, C, Castañera González, R, Huang, GC, Choudhary, P, Frost, G & Persaud, SJ 2017, 'The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro', Diabetes, Obesity and Metabolism, vol. 19, no. 2, pp. 257-265. https://doi.org/10.1111/dom.12811

The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. / Pingitore, Attilio; Chambers, Edward S.; Hill, Thomas; Maldonado, Inmaculada Ruz; Liu, Bo; Bewick, Gavin; Morrison, Douglas J.; Preston, Tom; Wallis, Gareth A.; Tedford, Catriona; Castañera González, Ramón; Huang, Guo Cai; Choudhary, Pratik; Frost, Gary; Persaud, Shanta J.

In: Diabetes, Obesity and Metabolism, Vol. 19, No. 2, 28.02.2017, p. 257-265.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro

AU - Pingitore, Attilio

AU - Chambers, Edward S.

AU - Hill, Thomas

AU - Maldonado, Inmaculada Ruz

AU - Liu, Bo

AU - Bewick, Gavin

AU - Morrison, Douglas J.

AU - Preston, Tom

AU - Wallis, Gareth A.

AU - Tedford, Catriona

AU - Castañera González, Ramón

AU - Huang, Guo Cai

AU - Choudhary, Pratik

AU - Frost, Gary

AU - Persaud, Shanta J.

N1 - DOM-16-0635-OP.R2

PY - 2017/2/28

Y1 - 2017/2/28

N2 - AimsDiet-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.Materials and MethodsFor 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.ResultsColonic 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.ConclusionsOur 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.

AB - AimsDiet-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.Materials and MethodsFor 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.ResultsColonic 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.ConclusionsOur 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.

KW - beta cell

KW - dietary intervention

KW - insulin secretion

KW - islets

KW - short chain fatty acids

KW - type 2 diabetes

U2 - 10.1111/dom.12811

DO - 10.1111/dom.12811

M3 - Article

VL - 19

SP - 257

EP - 265

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1463-1326

IS - 2

ER -