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.