Comparison of PEGylated FGF-21 with insulin glargine for long-lasting hypoglycaemic effect in db/db mice - 30/01/15

Doi : 10.1016/j.diabet.2014.09.001

X. Ye ^a, J. Qi ^a, Y. Wu ^a, D. Yu ^a, P. Xu ^a, S. Li ^a, S. Zhu ^c, Q. Wu ^a, G. Ren ^a, D. Li ^a,^b,^⁎
^a Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, 150030 Harbin, China
^b Key Laboratory of Agricultural Biological Functional Gene, Northeast Agricultural University, Harbin, China
^c School of Food Science and Technology, Jiangnan University, State Key Laboratory of Food Science and Technology, Wuxi, China

^⁎Corresponding author. Northeast Agricultural University, College of Life Science, No. 59, Mucai Street, Xiangfang District, 150030 Harbin, Heilongjiang, China. Tel.: +86 451 551 906 45; fax: +86 451 551 033 36.

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Abstract

Aim

This study investigated the long-acting antidiabetic efficacy of PEGylated fibroblast growth factor (FGF)-21 in type 2 diabetic db/db mice.

Methods

PEGylated FGF-21 was prepared by modifying the N-terminus of human FGF-21 (hFGF-21) using mPEG-ALD. To compare the long-lasting hypoglycaemic effects of PEGylated FGF-21 and insulin glargine in diabetic db/db mice, their pharmacological efficacy was evaluated by changes in blood glucose levels, body weight, insulin levels, glycosylated haemoglobin levels, lipid profile and liver function parameters, and by oral glucose tolerance tests (OGTTs).

Results

Both PEGylated FGF-21 and insulin glargine decreased plasma glucose in db/db mice. However, compared with insulin glargine treatment, PEGylated FGF-21 therapy had more significant effects in lowering blood glucose and glycosylated haemoglobin levels, improving lipid profile and liver function parameters, alleviating insulin resistance and reducing the glucose area under the curve in OGTTs.

Conclusion

Our results suggest that PEGylated FGF-21 is an ideal candidate as a long-acting antidiabetes drug, and holds significant promise as an effective therapeutic agent in the treatment of type 2 diabetes patients.

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Keywords : FGF-21, Insulin glargine, PEGylation, Diabetes, Hypoglycaemic effect

Esquema

Introduction

Materials and methods

Materials

Preparation of PEGylated FGF-21

Glucose uptake activity assay of PEGylated FGF-21

Administration of PEGylated FGF-21

Measuring the antidiabetic effects of PEGylated FGF-21

Statistical analysis

Results

Site-specific PEGylation of hFGF-21 and purification

Biological activity of PEGylated FGF-21 in vitro

PEGylated FGF-21 versus insulin glargine for long-lasting antidiabetic effects

PEGylated FGF-21 and insulin glargine effects on body weight and food intake

PEGylated FGF-21 and insulin glargine effects on OGTT results

PEGylated FGF-21 and insulin glargine effects on FBG and FINS

PEGylated FGF-21 and insulin glargine effects on glycosylated haemoglobin

PEGylated FGF-21 and insulin glargine effects on serum lipid and liver function

PEGylated FGF-21 and insulin glargine effects on glucose and lipid metabolism

Discussion

Disclosure of interest

Exportación

Vol 41 - N° 1

P. 82-90 - février 2015 Regresar al número

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Comparison of PEGylated FGF-21 with insulin glargine for long-lasting hypoglycaemic effect in db/db mice - 30/01/15

Abstract

Aim

Methods

Results

Conclusion

Esquema

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