Abstract
Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) have a similar but complementary role in regulating blood glucose level. This study was aimed to develop a functional-complementary dual insulinotropic peptide which releases both GLP-1 and GIP in vivo, and to investigate its therapeutic effect on type 2 diabetes in mice. We firstly constructed a vector pET-22b(+)-rolGG to express a recombinant oral long-acting GLP-1–GIP fusion peptide (rolGG) in E. coli. The rolGG peptide was then purified and confirmed its capacity of releasing recombinant oral long-acting GLP-1 (rolGLP-1) and recombinant GIP (rGIP) upon trypsin digestion in vitro, which were designed to resist in vivo enzymatic degradation. The therapeutic effect of rolGG was assessed in comparison with rolGLP-1 alone by daily oral-gavage administration up to 10 days in streptozotocin-induced type 2 diabetic mice. Saline and rosiglitazone administrations were served as negative and positive controls, respectively. The results showed that rolGG treatment decreased plasma glucose level by 26.7 and 46.3 % (p < 0.01), respectively, at 5 and 10 days after the initial oral-gavage. The rolGG treatment also led to a trend of body weight increase, drink level and food intake decrease (p < 0.05). In comparison, the oral administration of rolGLP-1 alone exhibited similar effects to rolGG with regard to plasma glucose level, drink level and food intake. In conclusion, we expressed and purified a dual insulinotropic peptide rolGG. Oral-gavage administration of rolGG showed a therapeutic effect on reduction of plasma glucose and alleviation of emaciation, polydipsia, and polyphagia symptoms in streptozotocin-induced diabetic mice.
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This study was supported by Project 863 of China (2008AA02Z205).
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Zhang, Y., Wang, W., Wei, Y. et al. Construction of a Functional-Complementary Dual Insulinotropic Peptide rolGG and Its Therapeutic Effect on Type 2 Diabetes. Int J Pept Res Ther 18, 327–333 (2012). https://doi.org/10.1007/s10989-012-9305-0
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DOI: https://doi.org/10.1007/s10989-012-9305-0