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

Autor: Xiaokun Li, Saisai Zhang, Zhichao Fan, Baile Wang, Xuebo Pan, Yanna Ye, Chaoming Wu, Qinyao Li, Yingying Pan, Zhuofeng Lin, Rongrong Xiong, Jujia Zheng, Fanghua Gong
Rok vydání: 2018
Předmět:
0301 basic medicine
medicine.medical_specialty
insulin
FGF21
medicine.medical_treatment
Apoptosis
03 medical and health sciences
Islets of Langerhans
Mice
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Internal medicine
Insulin-Secreting Cells
medicine
Animals
Secretion
Transcription factor
Protein kinase B
Pancreas
PI3K/AKT/mTOR pathway
Mice
Knockout
geography
geography.geographical_feature_category
diabetes
Chemistry
Pancreatic islets
Insulin
Cell Biology
Original Articles
Islet
Fibroblast Growth Factors
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Glucose
Diabetes Mellitus
Type 2
030220 oncology & carcinogenesis
pancreatic β‐cell
Molecular Medicine
Original Article
Insulin Resistance
Proto-Oncogene Proteins c-akt
Signal Transduction
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
Popis: Fibroblast 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.
Databáze: OpenAIRE
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