Acta Pharmacologica Sinica 2008 May; 29 (5): 573-579; doi: 10.1111/j.1745-7254.2008.00782.x

Aim: To investigate the effect of recombined human glucagon-like peptide 1 (rhGLP-1 [7-36]) on the secretion and expression of amylin in Goto-Kakizaki (GK) rats.

Methods: The GK rats were treated with rhGLP-1 (7-36) 56 and 133 µg·kg^-1 subcutaneously for 12 weeks. The fasting and post-prandial blood glucose levels were measured. The plasma amylin concentration was measured by ELISA. The transcription levels of amylin and insulin mRNA were evaluated by fluorescent-quantitative-PCR. Immunohistochemistry was utilized to detect the amylin protein. Histological examination was assayed by light microscopy.

Results: Treatment with rhGLP-1 (7-36) caused a significant reduction of post-prandial blood glucose levels in the GK rats (P<0.05). The plasma amylin levels of the GK rats were lower than those of Wistar rats after the glucose administration (P<0.01). Treatment with rhGLP-1 (7-36) exhibited a marked elevation of the glucose-stimulated plasma amylin level (P<0.05) and slight histological amelioration. The amylin expression was augmented in the rhGLP-1 (7-36)-treated GK rat pancreas. Amylin and insulin mRNA were also highly expressed in the treated GK rats (P<0.05). However, the ratio of amylin to insulin mRNA was significantly decreased by treatment with rhGLP-1 (7-36).

Conclusion: RhGLP-1 (7-36) stimulates the secretion and expression of amylin, and exerts a beneficial effect on the ratio of amylin to insulin mRNA. These findings suggest that GLP-1 and GLP-1 analogs are ideal candidates for the treatment of type 2 diabetes.

Keywords: amylin; islet amyloid polypeptide; insulin; glucagon-like peptide 1; Goto-Kakizaki rats; type 2 diabetes