Oral administration of a fusion protein containing eight GLP-1 analogues produced in Escherichia coli BL21(DE3) in streptozotocin-induced diabetic rats.
Glucagon-like peptide-1 (7-36) amide (GLP-1), a gut hormone released into the blood stream after feeding, can stimulate insulin secretion by potentiating the insulinotropic action of glucose. An expression vector pET-22bG8, encoding a fusion protein containing eight tandem repeat GLP-1 ([Ser(8), Gln(26), Asp(34)]-GLP-1) analogues, was constructed and transformed into the Escherichia coli BL21(DE3) strain over-expressing the His-tagged fusion protein under the IPTG promoter. SDS-PAGE and Western blot analysis demonstrated that the His-tagged GLP-1 fusion protein migrated as a single protein with a molecular weight of 32 kDa. Following chronic (10 days) oral administration (20 mg kg(-1) day(-1)) of the fusion protein to diabetic rats, serum glucose levels were significantly lowered from 26 +/- 2.5 to 7.9 +/- 1.4 mmol/l. Further studies are needed to evaluate the potential use for GLP-1 analogue short peptide in the treatment of diabetes mellitus.
Hou
Jianhua
J
The Key Laboratory for Bioactivematerial of Ministry of Education, Institute for Molecular Biology, College of Life Science, Nankai University, Tianjin, 300071, P.R. China.
Yan
Ruixiang
R
Ding
Dongfeng
D
Yang
Liquan
L
Wang
Cuiyan
C
Wu
Zhiqiang
Z
Yu
Xiaoju
X
Li
Weidong
W
Li
Minggang
M
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D013311:Streptozocin
D001786:Blood Glucose; D011993:Recombinant Fusion Proteins; D013311:Streptozocin; D052216:Glucagon-Like Peptide 1