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The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro
- Source :
- Pingitore, A, Chambers, E S, Hill, T, Maldonado, I R, Liu, B, Bewick, G, Morrison, D J, Preston, T, Wallis, G A, Tedford, C, Castañera González, R, Huang, G C, Choudhary, P, Frost, G & Persaud, S J 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 & metabolism, vol. 19, no. 2, pp. 257-265 . https://doi.org/10.1111/dom.12811
- Publication Year :
- 2017
-
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.
- Subjects :
- 0301 basic medicine
Male
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Apoptosis
Fatty Acids, Nonesterified
0302 clinical medicine
Endocrinology
Glucagon-Like Peptide 1
Insulin-Secreting Cells
Insulin Secretion
Glucose homeostasis
Insulin
chemistry.chemical_classification
Caspase 7
geography.geographical_feature_category
Caspase 3
Insulin secretion
Short-chain fatty acid
Inulin
Esters
Short chain fatty acids
Type 2 diabetes
Middle Aged
Islet
Immunohistochemistry
Beta cell
Female
Islets
Adult
medicine.medical_specialty
Colon
Blotting, Western
030209 endocrinology & metabolism
Receptors, Cell Surface
Biology
In Vitro Techniques
03 medical and health sciences
Islets of Langerhans
In vivo
Internal medicine
Internal Medicine
medicine
Humans
Aged
geography
Fatty acid
Fatty Acids, Volatile
Dietary Fats
Dietary intervention
030104 developmental biology
chemistry
Propionate
Propionates
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Pingitore, A, Chambers, E S, Hill, T, Maldonado, I R, Liu, B, Bewick, G, Morrison, D J, Preston, T, Wallis, G A, Tedford, C, Castañera González, R, Huang, G C, Choudhary, P, Frost, G & Persaud, S J 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 & metabolism, vol. 19, no. 2, pp. 257-265 . https://doi.org/10.1111/dom.12811
- Accession number :
- edsair.doi.dedup.....e281dd6a96f63b84bfda8836d9c040da