Open AccessPancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling‐dependent manner
Author(s) -
Pan Yingying,
Wang Baile,
Zheng Jujia,
Xiong Rongrong,
Fan Zhichao,
Ye Yanna,
Zhang Saisai,
Li Qinyao,
Gong Fanghua,
Wu Chaoming,
Lin Zhuofeng,
Li Xiaokun,
Pan Xuebo
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14007
Subject(s) - medicine , endocrinology , protein kinase b , insulin , fgf21 , glucose homeostasis , fibroblast growth factor , islet , biology , pi3k/akt/mtor pathway , pancreatic islets , insulin receptor , signal transduction , insulin oscillation , microbiology and biotechnology , insulin resistance , receptor
Fibroblast growth factor 21 ( FGF 21) is important in glucose, lipid homeostasis and insulin sensitivity. However, it remains unknown whether FGF 21 is involved in insulin expression and secretion that are dysregulated in type 2 diabetes mellitus (T2 DM ). In this study, we found that FGF 21 was down‐regulated in pancreatic islets of db/db mice, a mouse model of T2 DM , along with decreased insulin expression, suggesting the possible involvement of FGF 21 in maintaining insulin homeostasis and islet β‐cell function. Importantly, FGF 21 knockout exacerbated palmitate‐induced islet β‐cell failure and suppression of glucose‐stimulated insulin secretion ( GSIS ). Pancreatic FGF 21 overexpression significantly increased insulin expression, enhanced GSIS , improved islet morphology and reduced β‐cell apoptosis in db/db mice. Mechanistically, FGF 21 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 ( PI 3K)/Akt signaling in islets of db/db mice. In addition, pharmaceutical inhibition of PI 3K/Akt signaling effectively suppressed FGF 21‐induced expression of insulin gene transcription factors and SNARE proteins, suggesting an essential role of PI 3K/Akt signaling in FGF 21‐induced insulin expression and secretion. Taken together, our results demonstrate a protective role of pancreatic FGF 21 in T2 DM mice through inducing PI 3K/Akt signaling‐dependent insulin expression and secretion.