Short chain fatty acids stimulate insulin secretion and reduce apoptosis in mouse and human islets in vitro:Role of free fatty acid receptor 2

Autor: Inmaculada Ruz-Maldonado, Noemi González-Abuín, Shanta J. Persaud, Attilio Pingitore, Gary Frost, Guo Cai Huang
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Adult
Male
endocrine system
insulin secretion
Sodium Acetate
β-cell function
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
030209 endocrinology & metabolism
Caspase 3
Apoptosis
Receptors
Cell Surface
030204 cardiovascular system & hematology
Fatty Acids
Nonesterified
Receptors
G-Protein-Coupled
03 medical and health sciences
Islets of Langerhans
Mice
0302 clinical medicine
Endocrinology
Insulin-Secreting Cells
Free fatty acid receptor 2
Insulin Secretion
Internal Medicine
Medicine
Animals
Humans
Insulin
Receptor
Protein kinase C
Cells
Cultured
Mice
Knockout
islets
geography
geography.geographical_feature_category
Phospholipase C
business.industry
Middle Aged
Islet
Fatty Acids
Volatile
Cell biology
Mice
Inbred C57BL
insulin secretagogue
Female
type 2 diabetes
Propionates
business
Zdroj: Pingitore, A, Gonzalez-Abuin, N, Ruz-Maldonado, I, Huang, G C, Frost, G & Persaud, S J 2018, ' Short chain fatty acids stimulate insulin secretion and reduce apoptosis in mouse and human islets in vitro : Role of free fatty acid receptor 2 ', Diabetes, Obesity and Metabolism . https://doi.org/10.1111/dom.13529
DOI: 10.1111/dom.13529
Popis: Aims: To evaluate the role of free fatty acid receptor 2 (FFAR2)/G-protein coupled receptor 43 in mediating the effects of the short chain fatty acids (SCFAs) sodium acetate (SA) and sodium propionate (SP) on islet function in vitro, and to identify the intracellular signalling pathways used in SCFA-induced potentiation of glucose-induced insulin secretion. Materials and methods: Islets of Langerhans were isolated from wild-type and FFAR2−/− mice and from human donors without diabetes. The effects of SA and SP on dynamic insulin secretion from perifused islets were quantified by radioimmunoassay, signalling downstream of SCFAs was profiled by single-cell calcium microfluorimetry, and measurement of cAMP was performed using a fluorescence assay. Islet apoptosis was induced by exposure to cytokines or sodium palmitate, and the effects of SA and SP in regulating islet apoptosis were assessed by quantification of caspase 3/7 activities. Results: Deletion of FFAR2 did not affect islet morphology or insulin content. SA and SP reversibly potentiated insulin secretion from mouse islets in a FFAR2-dependent manner. SCFA-induced potentiation of insulin secretion was coupled to Gq activation of phospholipase C and protein kinase C, with no evidence of Gi-mediated signalling. SA and SP protected human and mouse islets from apoptosis, and these pro-survival properties were dependent on islet expression of FFAR2. Conclusion: Our results indicate that FFAR2 directly mediates both the stimulatory effects of SA and SP on insulin secretion and their protection against islet apoptosis. We have also shown that SCFA coupling in islets occurs via Gq-coupled intracellular signalling.
Databáze: OpenAIRE
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