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


CONCLUSIONS
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.
Weng
Hong-Bo
HB
Department of Pharmacology, School of Pharmacy, ZhongshanHospital, Fudan University, Shanghai 200032, China.
Gu
Qian
Q
Liu
Meng
M
Cheng
Neng-Neng
NN
Li
Duan
D
Gao
Xin
X
D000682:Amyloid / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004435:Eating; D005215:Fasting; D015870:Gene Expression / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D058228:Islet Amyloid Polypeptide; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D012333:RNA, Messenger; D011994:Recombinant Proteins; D052216:Glucagon-Like Peptide 1; D005947:Glucose