ArticleJournal of cellular and molecular medicine2019
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.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Circulating fibroblast growth factor 21 levels in gestational diabetes mellitus and preeclampsia: a systematic review and meta-analysis.BMC pregnancy and childbirth · 2025Pooled it
- Contribution of Liver and Pancreatic Islet Crosstalk to β-Cell Function/Dysfunction in the Presence of Fatty Liver.Frontiers in endocrinology · 2022Pooled it
- Efficiency of afamin and fibroblast growth factor 21 for early prediction of gestational diabetes mellitus.Scientific reports · 2026Article
- Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.Biomolecules · 2026Review
- Association of Changes in Portal Insulin with Immunometabolism During and After Hepatitis C Virus Infection.Journal of clinical and translational hepatology · 2026Article
- Functions of FGF21 and its role in cardiac hypertrophy.Journal of advanced research · 2026Review
- Article
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- FGF21 protects against HFpEF by improving cardiac mitochondrial bioenergetics in mice.Nature communications · 2025Article
- The role of the glucagon-FGF21 axis in improving beta cell function during glucose intolerance and SGLT2 inhibition.Diabetes, obesity & metabolism · 2025Article
- Enhanced Insulin Secretion Through Upregulation of Transcription Factors by Hydroalcoholic Extract of Securigera securidaca Seeds in Diabetic Animal Model.Endocrinology, diabetes & metabolism · 2024Article
- Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network.Genes & diseases · 2024Review
- Exploring exercise-driven exerkines: unraveling the regulation of metabolism and inflammation.PeerJ · 2024Review
- Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity.Frontiers in immunology · 2024Review
- Batokine in Central Nervous System Diseases.Molecular neurobiology · 2023Review
- Differential disruption on glucose and insulin metabolism in two rat models of diet-induced obesity, based on carbohydrates or lipids.Molecular and cellular biochemistry · 2023Article
- Hepatic-Specific FGF21 Knockout Abrogates Ovariectomy-Induced Obesity by Reversing Corticosterone Production.International journal of molecular sciences · 2023Article
- Increased hepatic Akt phosphorylation alleviated glucose intolerance and improved liver function in leptin-deficient mice.Clinical and experimental hepatology · 2023Article
- FGF-23 protects cell function and viability in murine pancreatic islets challenged by glucolipotoxicity.Pflugers Archiv : European journal of physiology · 2023Article
- Pancreatic alpha cell glucagon-liver FGF21 axis regulates beta cell regeneration in a mouse model of type 2 diabetes.Diabetologia · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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