GLP-1 Alleviates Diabetic Kidney Disease Through Activation of Autophagy by Regulating AMPK/mTOR Pathway.

GLP-1 Alleviates Diabetic Kidney Disease Through Activation of Autophagy by Regulating AMPK/mTOR Pathway. Am J Physiol Endocrinol Metab. 2020 Sep 28;: Authors: Yang S, Lin C, Zhuo X, Wang J, Rao S, Xu W, Cheng Y, Yang L Abstract Glucagon-like peptide-1 (GLP-1) is a novel anti-diabetic agent used in clinical practice. Recently, it was reported to exert a renoprotective effect in the HK-2 cells and kidneys of diabetic rats, which was induced by one type of GLP-1 analogues liraglutide in the presence of high glucose. However, most of the previous findings mainly focused on its indirect effect in inhibiting the advanced glycation end products. Here, besides glycemic control, we also demonstrated a stimulatory role of liraglutide in promoting autophagy and relieving oxidative stress in Zucker diabetic fatty(ZDF) rats. The renoprotective effect of liraglutide has been demonstrated by significantly decreasing urinary albumin (P<0.01) and ameliorating renal pathological changes (P<0.001) in vivo. Besides that, proliferation of Hkc8 and HEK293 cells have been increased after treating with exendin-4, a GLP-1 receptor agonist. Moreover, the GLP-1 could positively improve the progression of autophagy in vivo and in vitro through regulating the autophagy-related protein LC3 and P62 via AMPK/mTOR signaling pathway. Simultaneously, it could reverse Nrf2 translocation into the nuclei, then suppress oxidative stress. In terms of mechanism, the ...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research