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KMID : 0624620130460120606
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BMB Reports
2013 Volume.46 No. 12 p.606 ~ p.610
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Novel AGLP-1 albumin fusion protein as a long-lasting agent for type 2 diabetes
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Kim Yong-Mo
Lee Sang-Mee
Chung Hye-Shin
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Abstract
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Glucagon like peptide-1 (GLP-1) regulates glucose mediated-insulin secretion, nutrient accumulation, and β-cell growth. Despite the potential therapeutic usage for type 2 diabetes (T2D), GLP-1 has a short half-life in vivo (t(1/2) <2 min). In an attempt to prolong half-life, GLP-1 fusion proteins were genetically engineered: GLP-1 human serum albumin fusion (GLP-1/HSA), AGLP-1/HSA which has an additional alanine at the N-terminus of GLP-1, and AGLP-1-L/HSA, in which a peptide linker is inserted between AGLP-1 and HSA. Recombinant fusion proteins secreted from the Chinese Hamster Ovary-K1 (CHO-K1) cell line were purified with high purity (>96%). AGLP-1 fusion protein was resistant against the dipeptidyl peptidase-IV (DPP-IV). The fusion proteins activated cAMP-mediated signaling in rat insulinoma INS-1 cells. Furthermore, a C57BL/6N mice pharmacodynamics study exhibited that AGLP-1-L/HSA effectively reduced blood glucose level compared to AGLP-1/HSA.
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KEYWORD
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Dipeptidyl peptidase-IV, Fusion protein, Glucagon like peptide-1, Human serum albumin, Type 2 diabetes
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