Effect of liraglutide on endoplasmic reticulum stress in the renal tissue of type 2 diabetic rats

BACKGROUND: Liraglutide is a glucagon-like peptide 1 receptor agonist analog that has been found to have a therapeutic effect in diabetes. In addition to its ability to treat diabetes, liraglutide has beneficial effects on the cardiovascular system and kidney as well as other beneficial effects, but its specific mechanism is not clear. In this study, a rat model of type 2 diabetes was established by administration of a high-sugar, high-fat diet combined with low-dose streptozotocin (STZ) to observe the effect of liraglutide on the kidneys of type 2 diabetes rats and the possible underlying mechanisms. AIM: To explore whether liraglutide has a protective effect on type 2 diabetic rat kidneys and the underlying mechanisms. METHODS: Eight-week-old male Sprague-Dawley rats were randomly divided into a control group, model group, low-dose liraglutide group, and high-dose liraglutide group. Control rats were fed a standard diet, while model group and intervention group rats were fed high-sugar, high-fat feed for 1 mo and then intraperitoneally injected with 40 mg/kg STZ to induce type 2 diabetes. The low-dose and high-dose intervention groups received 100 µg/kg and 200 µg/kg liraglutide, respectively, once daily by subcutaneous injection. The control and model groups were given an equivalent volume of physiological saline for 8 wk. Pathological changes in renal tissues were observed by hematoxylin and eosin staining and periodic acid-Schiff staining, and GRP78 and caspase-12 expression was detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Western blot analysis showed that GRP78 and caspase-12 protein expression in kidney tissue was significantly higher in model rats than in normal rats and lower in the liraglutide-treated groups than in the model group, with a more significant decrease being observed in the high-dose group than in the low-dose group. RT-PCR showed that the mRNA expression of GRP78 and caspase-12 was higher in model rats than in control rats and lower in the liraglutide-treated groups than in the model group, with the high-dose group exhibiting a more significant decrease than the low-dose group. CONCLUSION: Liraglutide may delay the progression of diabetic nephropathy by reducing endoplasmic reticulum stress and protect the kidneys in a dose-dependent manner.