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.