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Article: Pancreatic Fibroblast Growth Factor 21 Protects Against Type 2 Diabetes In Mice By Promoting Insulin Expression And Secretion In A Pi3k/akt Signaling-dependent Manner

TitlePancreatic Fibroblast Growth Factor 21 Protects Against Type 2 Diabetes In Mice By Promoting Insulin Expression And Secretion In A Pi3k/akt Signaling-dependent Manner
Authors
KeywordsDiabetes
FGF21
Insulin
Pancreatic β-cell
Issue Date2019
PublisherWiley Open Access for Foundation for Cellular and Molecular Medicine. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838
Citation
Journal of Cellular and Molecular Medicine, 2019, v. 23 n. 2, p. 1059-1071 How to Cite?
AbstractFibroblast growth factor 21 (FGF21) is important in glucose, lipid homeostasis and insulin sensitivity. However, it remains unknown whether FGF21 is involved in insulin expression and secretion that are dysregulated in type 2 diabetes mellitus (T2DM). In this study, we found that FGF21 was down‐regulated in pancreatic islets of db/db mice, a mouse model of T2DM, along with decreased insulin expression, suggesting the possible involvement of FGF21 in maintaining insulin homeostasis and islet β‐cell function. Importantly, FGF21 knockout exacerbated palmitate‐induced islet β‐cell failure and suppression of glucose‐stimulated insulin secretion (GSIS). Pancreatic FGF21 overexpression significantly increased insulin expression, enhanced GSIS, improved islet morphology and reduced β‐cell apoptosis in db/db mice. Mechanistically, FGF21 promoted expression of insulin gene transcription factors and soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) proteins, the major regulators of insulin secretion, as well as activating phosphatidylinositol 3‐kinase (PI3K)/Akt signaling in islets of db/db mice. In addition, pharmaceutical inhibition of PI3K/Akt signaling effectively suppressed FGF21‐induced expression of insulin gene transcription factors and SNARE proteins, suggesting an essential role of PI3K/Akt signaling in FGF21‐induced insulin expression and secretion. Taken together, our results demonstrate a protective role of pancreatic FGF21 in T2DM mice through inducing PI3K/Akt signaling‐dependent insulin expression and secretion.
Persistent Identifierhttp://hdl.handle.net/10722/275102
ISSN
2019 Impact Factor: 4.486
2015 SCImago Journal Rankings: 1.941
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPan, Y-
dc.contributor.authorWang, B-
dc.contributor.authorZheng, J-
dc.contributor.authorXiong, R-
dc.contributor.authorFan, Z-
dc.contributor.authorYe, Y-
dc.contributor.authorZhang, S-
dc.contributor.authorLi, Q-
dc.contributor.authorGong, F-
dc.contributor.authorWu, C-
dc.contributor.authorLin, Z-
dc.contributor.authorLi, X-
dc.contributor.authorPan, X-
dc.date.accessioned2019-09-10T02:35:30Z-
dc.date.available2019-09-10T02:35:30Z-
dc.date.issued2019-
dc.identifier.citationJournal of Cellular and Molecular Medicine, 2019, v. 23 n. 2, p. 1059-1071-
dc.identifier.issn1582-1838-
dc.identifier.urihttp://hdl.handle.net/10722/275102-
dc.description.abstractFibroblast growth factor 21 (FGF21) is important in glucose, lipid homeostasis and insulin sensitivity. However, it remains unknown whether FGF21 is involved in insulin expression and secretion that are dysregulated in type 2 diabetes mellitus (T2DM). In this study, we found that FGF21 was down‐regulated in pancreatic islets of db/db mice, a mouse model of T2DM, along with decreased insulin expression, suggesting the possible involvement of FGF21 in maintaining insulin homeostasis and islet β‐cell function. Importantly, FGF21 knockout exacerbated palmitate‐induced islet β‐cell failure and suppression of glucose‐stimulated insulin secretion (GSIS). Pancreatic FGF21 overexpression significantly increased insulin expression, enhanced GSIS, improved islet morphology and reduced β‐cell apoptosis in db/db mice. Mechanistically, FGF21 promoted expression of insulin gene transcription factors and soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) proteins, the major regulators of insulin secretion, as well as activating phosphatidylinositol 3‐kinase (PI3K)/Akt signaling in islets of db/db mice. In addition, pharmaceutical inhibition of PI3K/Akt signaling effectively suppressed FGF21‐induced expression of insulin gene transcription factors and SNARE proteins, suggesting an essential role of PI3K/Akt signaling in FGF21‐induced insulin expression and secretion. Taken together, our results demonstrate a protective role of pancreatic FGF21 in T2DM mice through inducing PI3K/Akt signaling‐dependent insulin expression and secretion.-
dc.languageeng-
dc.publisherWiley Open Access for Foundation for Cellular and Molecular Medicine. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838-
dc.relation.ispartofJournal of Cellular and Molecular Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectDiabetes-
dc.subjectFGF21-
dc.subjectInsulin-
dc.subjectPancreatic β-cell-
dc.titlePancreatic Fibroblast Growth Factor 21 Protects Against Type 2 Diabetes In Mice By Promoting Insulin Expression And Secretion In A Pi3k/akt Signaling-dependent Manner-
dc.typeArticle-
dc.identifier.emailWang, B: baile612@hku.hk-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1111/jcmm.14007-
dc.identifier.pmid30461198-
dc.identifier.pmcidPMC6349243-
dc.identifier.scopuseid_2-s2.0-85056888091-
dc.identifier.hkuros304288-
dc.identifier.volume23-
dc.identifier.issue2-
dc.identifier.spage1059-
dc.identifier.epage1071-
dc.identifier.isiWOS:000459729900033-
dc.publisher.placeUnited Kingdom-

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