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∆nFGF1 Protects β-Cells against High Glucose-Induced Apoptosis via the AMPK/SIRT1/PGC-1α Axis

Qiong Chen^1,2, Xinwei Chen², Zhenyu Jia²

¹Pingyang Affiliated Hospital of Wenzhou Medical University, Zhejiang 325400, China.

Oxidative Medicine and Cellular Longevity

|October 13, 2022

Abstract:

Long-term exposure to high glucose leads to β-cell dysfunction and death. Fibroblast growth factor 1 (FGF1) has emerged as a promising diabetes treatment, but its pharmaceutical role and mechanism against glucolipotoxicity-induced β-cell dysfunction remain uncharacterized. Wild-type FGF1 (FGF1^WT) may exhibit in vivo mitogenicity, but deletion of N-terminal residues 1-27 gives a nonmitogenic variant, ∆nFGF1, that does not promote cell proliferation and still retains the metabolic activity of FGF1^WT. To investigate the roles of ∆nFGF1 on glucose regulation and potential islet β-cell dysfunction, db/db mice were used as a model of type 2 diabetes. The results showed that insulin secretion and apoptosis of islet β-cells were dramatically improved in ∆nFGF1-treated db/db mice. To further test the effects of ∆nFGF1 treatment, pancreatic β-cell (MIN6) cells were exposed to a mixture of palmitic acid (PA) and high glucose (HG) to mimic glucolipotoxic conditions in vitro. Treatment with ∆nFGF1 significantly inhibited glucolipotoxicity-induced apoptosis. Mechanistically, ∆nFGF1 exerts a protective effect on β-cells via activation of the AMPK/SIRT1/PGC-1α signaling pathway. These findings demonstrate that ∆nFGF1 protects pancreatic β-cells against glucolipotoxicity-induced dysfunction and apoptosis.

Insights

A modified Fibroblast Growth Factor 1 (∆nFGF1) protects pancreatic beta cells from high glucose and fat-induced damage. This finding offers a new therapeutic strategy for diabetes by improving insulin secretion and reducing cell death.

Area of Science:

Endocrinology
Molecular Biology
Cell Biology

Background:

Long-term high glucose exposure impairs pancreatic beta-cell function and survival.
Fibroblast Growth Factor 1 (FGF1) shows potential for diabetes treatment, but its specific mechanism against glucolipotoxicity is unclear.
A non-mitogenic variant, ∆nFGF1, retains metabolic activity and is investigated for its therapeutic potential.

Purpose of the Study:

To investigate the effects of ∆nFGF1 on glucose regulation and islet beta-cell dysfunction in a type 2 diabetes model.
To elucidate the protective mechanism of ∆nFGF1 against glucolipotoxicity in pancreatic beta cells.

Main Methods:

Utilized *db/db* mice as a model for type 2 diabetes.
Treated MIN6 cells with palmitic acid and high glucose to induce glucolipotoxicity *in vitro*.
Analyzed the activation of the AMPK/SIRT1/PGC-1α signaling pathway.

Main Results:

∆nFGF1 treatment significantly improved insulin secretion and reduced apoptosis in islet beta cells of *db/db* mice.
∆nFGF1 inhibited apoptosis in MIN6 cells exposed to glucolipotoxic conditions.
∆nFGF1 protected beta cells by activating the AMPK/SIRT1/PGC-1α signaling pathway.

Conclusions:

∆nFGF1 demonstrates a protective effect on pancreatic beta cells against glucolipotoxicity-induced dysfunction and apoptosis.
∆nFGF1 represents a promising therapeutic agent for managing type 2 diabetes by preserving beta-cell function.

Read full analysis

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