title: Novel AGLP-1 albumin fusion protein as a long-lasting agent for type 2 diabetes.
abstract: 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.
authors.forename: Yong-Mo
authors.initials: YM
authors.lastname: Kim
authors.forename: Sang Mee
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Alteogen Inc., Bioventure Town, Daejeon 305-812; Department of Biotechnology, Hannam University, Daejeon 305-811, Korea hschung@hnu.kr.
authors.forename: Hye-Shin
authors.initials: HS
authors.lastname: Chung
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000493:pharmacokinetics; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D000409:Alanine