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

Acta Pharmacol Sin. 2008 May;29(5):573-9. doi: 10.1111/j.1745-7254.2008.00782.x.

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 mug/kg 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / blood*
  • Amyloid / genetics
  • Amyloid / metabolism*
  • Animals
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Eating
  • Fasting
  • Gene Expression / drug effects*
  • Glucagon-Like Peptide 1 / genetics
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucose / pharmacology
  • Humans
  • Hypoglycemic Agents / metabolism
  • Immunohistochemistry
  • Insulin / metabolism
  • Islet Amyloid Polypeptide
  • Male
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Time Factors

Substances

  • Amyloid
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Islet Amyloid Polypeptide
  • RNA, Messenger
  • Recombinant Proteins
  • Glucagon-Like Peptide 1
  • Glucose