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Long-lasting hypoglycemic effect of modified FGF-21 analog with polyethylene glycol in type 1 diabetic mice and its

Xianlong Ye1, Jianying Qi2, Qiang Wu3

  • 1College of Life Science, Henan Normal University, No. 46 Construction Road, 453007 Xinxiang, Henan Province, China.

European Journal of Pharmacology
|April 20, 2016
PubMed

Insights

PEGylation of fibroblast growth factor-21 (FGF-21) improved its stability and enhanced its long-lasting blood sugar-lowering effects in type 1 diabetic mice. This modified FGF-21 shows potential as a diabetes mellitus therapy.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Endocrinology

Background:

  • Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with therapeutic potential for diabetes mellitus.
  • Wild-type FGF-21 exhibits limitations in clinical application due to low bio-stability and hypoglycemic potency.

Purpose of the Study:

  • To enhance the therapeutic properties of FGF-21 through site-specific PEGylation.
  • To evaluate the in vitro and in vivo efficacy and safety of PEGylated FGF-21 (PEG-mFGF-21) for type 1 diabetes treatment.

Main Methods:

  • Site-specific PEGylation of N-terminus FGF-21 analog (mFGF-21) using mPEG-ALD.
  • Isolation of PEG-mFGF-21 via Capto Q anion exchange chromatography.
  • Assessment of in vitro bio-stability, biological activity, anti-diabetic effects in STZ-induced diabetic mice, and preliminary safety in healthy mice.

Main Results:

  • PEG-mFGF-21 demonstrated similar glucose uptake stimulation in HepG2 cells compared to mFGF-21.
  • PEGylation significantly enhanced anti-protease ability and prolonged the anti-diabetic effect in type 1 diabetic mice.
  • Preliminary safety assessment showed no subacute toxicity in healthy mice.

Conclusions:

  • PEGylation effectively improves the long-lasting hypoglycemic effect of mFGF-21 while preserving its in vitro biological activity.
  • PEG-mFGF-21 is a promising therapeutic candidate for type 1 diabetes treatment.
Keywords:
FGF-21PEGylationStabilityToxicityType 1 diabetes

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