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Volume 27, Issue 18
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

In our previous studies, it was found that metformin can elevate the expression of FGF21 in the peripheral blood of type 2 diabetic rats and improve insulin sensitivity in diabetic rats. However, whether this effect is mediated by increased FGF21 expression in pancreatic islet β-cells is still unknown. Therefore, this study focuses on the effect of metformin on insulin secretion in pancreatic β-cells.

Aims

Metformin can effectivly improve insulin resistance. Metformin influencing pancreatic β-cell function is inclusive. In this study, we sought to analyze possible variations in insulin secretion and possible signaling mechanisms after metformin intervention.

Methods

The study employed an model of a high-fat diet in streptozocin-induced diabetic rats and an model of rat pancreatic β-cells (INS-1 cells) that were subjected to damage caused by hyperglycemia and hyperlipidemia. After treating INS-1 cells in normal, high-glucose, and high-glucose+metformin, we measured insulin secretion by glucose-stimulated insulin secretion (GSIS). Insulin was measured using an enzyme-linked immunosorbent assay. FGF21 expression was detected by RT-PCR and Western blot, as well as that p-Akt and t-Akt expression were detected by Western blot in INS-1 cells and diabetic rat islets. Finally, to verify the regulation of the FGF21 /Akt axis in metformin administration, additional experiments were carried out in metformin-stimulated INS-1 cells.

Results

High-glucose could significantly stimulate insulin secretion while metformin preserved insulin secretion. Expression of FGF21 and p-Akt was decreased in high-glucose, however, metformin could reverse this effect in INS-1 cells and diabetic rat islets.

Conclusion

Our results demonstrate a protective role of metformin in preserving insulin secretion through FGF21/Akt signaling in T2DM.

© 2024 Bentham Science Publishers
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2023-10-19
2025-01-12

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Metformin Preserves Insulin Secretion in Pancreatic β-cells through FGF21/Akt Pathway In vitro and In vivo
Comb Chem High Throughput Screen 27, 2691 (2024); https://doi.org/10.2174/0113862073246747230920170201
/content/journals/cchts/10.2174/0113862073246747230920170201
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  • Article Type:     Research Article
Keyword(s): FGF21; GSIS; insulin secretion; metformin; p-Akt; Type 2 diabetes

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