Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway

Purpose. To explore the regulatory effects of liraglutide on the kidney and liver through the miR-34a/SIRT1 pathway with related factors in diabetic nephropathy (DN) rats. Methods. DN rats were randomly divided into two groups (n=10) and were injected with liraglutide or normal saline twice a day. T...

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Main Authors: Shan Xiao, Ye Yang, Yue-Tong Liu, Jun Zhu
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2021/8873956
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author Shan Xiao
Ye Yang
Yue-Tong Liu
Jun Zhu
author_facet Shan Xiao
Ye Yang
Yue-Tong Liu
Jun Zhu
author_sort Shan Xiao
collection DOAJ
description Purpose. To explore the regulatory effects of liraglutide on the kidney and liver through the miR-34a/SIRT1 pathway with related factors in diabetic nephropathy (DN) rats. Methods. DN rats were randomly divided into two groups (n=10) and were injected with liraglutide or normal saline twice a day. The 24-hour urine microalbumin content and biochemical index levels were measured. qRT-PCR was performed to detect the expression of miR-34a in the kidney and liver tissues. The levels of SIRT1, HIF-1a, Egr-1, and TGF-β1 in kidney and liver tissues were determined using qRT-PCR, western blot, and immunohistochemistry. Electron microscopy and HE staining were used to observe the ultrastructure and pathological changes. Results. Liraglutide treatment in DN rats decreased blood glucose, 24-hour urine microalbumin, TC, TG, LDL-C, UA, Cr, UREA, ALT, and AST levels and increased the level of HDL-C (P<0.05). Compared with the control group, the miR-34a levels were significantly decreased in kidney and liver tissues followed by liraglutide treatment (P<0.05). The levels of SIRT1 in the liraglutide group are significantly higher than those in the control group with the kidney and liver tissues (P<0.05). Conversely, the contents of HIF-1a, Egr-1, and TGF-β1 were significantly lower in the liraglutide group than in the control group (P<0.05). Electron microscopy showed that the kidney of the liraglutide-treated group exhibited minor broadening of the mesangial areas, fewer deposits, and a well-organized foot process. HE staining revealed that the kidney of the liraglutide-treated rats had a more regular morphology of the glomerulus and Bowman sac cavity and lighter tubular edema. Additionally, the liraglutide-treated DN rats had a clear hepatic structure, a lower degree of steatosis, and mild inflammatory cell infiltration. Conclusion. Liraglutide, through its effect on the miR-34a/SIRT1 pathway, may have a protective role in the kidney and liver of DN rats.
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spelling doaj-art-e96a1fe20e1d470f8cdf7cc66e10a0bd2025-02-03T05:49:15ZengWileyJournal of Diabetes Research2314-67452314-67532021-01-01202110.1155/2021/88739568873956Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 PathwayShan Xiao0Ye Yang1Yue-Tong Liu2Jun Zhu3Department of Endocrinology, People’s Hospital of Shenzhen Baoan District, The Second School of Clinical Medicine, Southern Medical University, The Second Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of No. 1 Cadres, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, ChinaDepartment of Ultrasonic ECG, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, ChinaDepartment of Endocrinology, People’s Hospital of Shenzhen Baoan District, The Second School of Clinical Medicine, Southern Medical University, The Second Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaPurpose. To explore the regulatory effects of liraglutide on the kidney and liver through the miR-34a/SIRT1 pathway with related factors in diabetic nephropathy (DN) rats. Methods. DN rats were randomly divided into two groups (n=10) and were injected with liraglutide or normal saline twice a day. The 24-hour urine microalbumin content and biochemical index levels were measured. qRT-PCR was performed to detect the expression of miR-34a in the kidney and liver tissues. The levels of SIRT1, HIF-1a, Egr-1, and TGF-β1 in kidney and liver tissues were determined using qRT-PCR, western blot, and immunohistochemistry. Electron microscopy and HE staining were used to observe the ultrastructure and pathological changes. Results. Liraglutide treatment in DN rats decreased blood glucose, 24-hour urine microalbumin, TC, TG, LDL-C, UA, Cr, UREA, ALT, and AST levels and increased the level of HDL-C (P<0.05). Compared with the control group, the miR-34a levels were significantly decreased in kidney and liver tissues followed by liraglutide treatment (P<0.05). The levels of SIRT1 in the liraglutide group are significantly higher than those in the control group with the kidney and liver tissues (P<0.05). Conversely, the contents of HIF-1a, Egr-1, and TGF-β1 were significantly lower in the liraglutide group than in the control group (P<0.05). Electron microscopy showed that the kidney of the liraglutide-treated group exhibited minor broadening of the mesangial areas, fewer deposits, and a well-organized foot process. HE staining revealed that the kidney of the liraglutide-treated rats had a more regular morphology of the glomerulus and Bowman sac cavity and lighter tubular edema. Additionally, the liraglutide-treated DN rats had a clear hepatic structure, a lower degree of steatosis, and mild inflammatory cell infiltration. Conclusion. Liraglutide, through its effect on the miR-34a/SIRT1 pathway, may have a protective role in the kidney and liver of DN rats.http://dx.doi.org/10.1155/2021/8873956
spellingShingle Shan Xiao
Ye Yang
Yue-Tong Liu
Jun Zhu
Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway
Journal of Diabetes Research
title Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway
title_full Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway
title_fullStr Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway
title_full_unstemmed Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway
title_short Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway
title_sort liraglutide regulates the kidney and liver in diabetic nephropathy rats through the mir 34a sirt1 pathway
url http://dx.doi.org/10.1155/2021/8873956
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