Increased secretion and expression of amylin in spontaneously diabetic Goto-Kakizaki rats treated with rhGLP-1 (7–36)
Abstract
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.
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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.