GLP-1R agonist may activate pancreatic stellate cells to induce rat pancreatic tissue lesion.
OBJECTIVE
To explore the mechanism of GLP-1R agonist-induced rat pancreatic tissue lesion.


METHODS
Thirty SD male rats were divided into three groups, namely GLP-1R agonist experimental group, diabetes-model experimental group and control group. Diabetes-model rats were induced by streptozotocin and high-sugar high-fat diet. GLP-1R agonist group and diabetes-model group were administered with GLP-1R agonist in dose 5 μg/kg each time, twice a day. After 10 weeks of treatment, the amount of matrix metalloproteinase (MMP)-2 and MMP-9, and expression of α-smooth muscle actin (α-SMA) and type III collagen protein in pancreatic tissue were measured.


RESULTS
The amount of MMP-2 and MMP-9 in GLP-1R agonist group and diabetes-model group were significantly higher than the control group. Compared with the GLP-1R agonist group, the diabetic model group had more severe pathological changes of pancreatic tissue interstitial edema, inflammatory cell infiltration, glandular atrophy and fibrosis, and significantly increased pancreatic tissue MMP-2 and MMP-9 levels, significantly increased α-SMA and collagen III-positive cell counts, all the differences were statistically significant. α-SMA and type III collagen were expressed in all parts of the lesions of GLP-1R agonist group and diabetes-model group. α-SMA can only be observed in the vessel wall in control group, however, in the other two groups, α-SMA can also be observed in pancreatic acinar cell interstitia, in addition to vessel wall.


CONCLUSIONS
Long-term subcutaneous GLP-1R agonist injection may activate pancreatic stellate cells, causing the expression of α-SMA and collagen III and the amount of MMP-2 and MMP-9 in pancreatic acinar cell interstitial significantly increasing, and thus inducing chronic inflammatory change.
General Surgery Department, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
Yongchao
Y
Yang
Xiao
X
Yu
Lihua
L
Huang
Can
C
Yu
D000818:Animals; D024061:Collagen Type III / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D010179:Pancreas / Q000378:metabolism; D058954:Pancreatic Stellate Cells / Q000187:drug effects*; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014688:Venoms / Q000494:pharmacology*
D024061:Collagen Type III; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
GLP-1R agonist; Histopathology; Pancreatic stellate cell