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논문분류	춘계학술대회 초록집
제목	Proximal tubular GLP-1 receptor activity is increased in CKD rat with myocardial infarction which enhanced after linagliptin
저자	Seung Jung Kim* 1, Kyung Min Kim1, Sun Moon Kim1, Hye-Young Kim1, Soon Kil Kwon1
출판정보	2016; 2016(1):
키워드	Chronic kidney disease, CKD rat model, GLP-1 receptor, linagliptin, myocardial infarction
초록	Background: Chronic kidney disease (CKD) is an important risk of ischemic heart disease and makes atherosclerosis. Glucagon like peptidase-1 (GLP-1) is an incretin hormone that enhances insulin secretion and GLP-1 agonist is used for glycemic control in patient with type 2 diabetes. Renal GLP-1 activity is increased in the chronic kidney disease, also GLP-1Receptor (GLP-1R) activation is related with cardiovascular protection. DPP4 inhibitor increases GLP-1 activity and known to protect heart and vessels. We investigated difference of renal GLP-1 activity in the CKD rat model with ischemic reperfusion and myocardial infarction model. Also, we tried to find the change of GLP-1 receptor activity after DPP-4 inhibitor. Methods: Adult Sprague Dawley rat was used for CKD rat model with 5 animals each group. The lower and upper thirds of the left kidney were resected. After 1 week, the right kidney was removed. For myocardial ischemia, left anterior descending coronary artery was ligated 2 weeks after 5/6 nephrectomy. 30 Minutes after ligation, we released ligated vessel for reperfusion model and kept ligation for MI model. We did shame operation to same numbers of animals. CKD and Myocardial ischemia rat were treated with oral linagliptin (5 mg/kg/day) from after surgery, renal and myocardial tissue of GLP-1R was measured via immunohistochemistry and Western blot (WB) analysis. Results: Renal cortical WB density of GLP-1R was increased 2 weeks after 5/6 nephrectomy then decreased in 4 weeks. Relative intensity standardized by beta-actin were 100 ± 10.2 (control), 161.2 ± 3.4 (2 wks, p<0.05), 102.7 ± 5.3 (4 wks), 48.6 ± 2.9 (8 wks, p<0.05) each. Immunohistochemistry findings were similar with WB. Peak intensity was noted 2 weeks later, then decreased after 4 weeks of surgery then stain was disappeared in 8 weeks after surgery. Linagliptin treated group showed significantly increased GLP-1R (2 wks, 154.4 ± 3.0; 2wks-Lina, 178.1 ± 0.1; 4 wks, 97.0 ± 0.4; 4wks-Lina, 127.8 ± 7.4 vs. C, 100.0 ± 0.3; p<0.05). After 1 week of ischemic injury, GLP-1R in CKD with MI and CKD with ischemic reperfusion were significantly increased. WB of GLP-1R was increased in the ischemic reperfusion rats, but decreased in CKD-MI model. However, it was increased in infarcted area after linagliptin. Comparing ischemic reperfusion injury, WB of CKD-MI model was significantly increased (43.3 ± 0.1 vs. 20.1 ± 12.5; p<0.05). Conclusion: Rena GLP-1R is increased in 2 wks of CKD and CKD-MI model. Proximal tubular GLP-1R expression is increased in CKD-MI model comparing with ischemic reperfusion. Altogether, these results suggest that expression of GLP-1 in kidney has a role in renal disease progression and GLP-1 activity may provide reno- protective effects independent of its hypoglycemic effects. Linagliptin can increase renal GLP-1R in CKD with MI rat model.
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