The kidneys release glucose into the systemic circulation through glucose reabsorption and renal gluconeogenesis. Currently, the significance of renal glucose release in pathological conditions has become a subject of interest. We examined the effect of sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i) on renal gluconeogenic enzyme expression in obese rats. Male Wistar rats (180–200 g) were fed either a normal diet (ND, n = 6) or a high-fat diet. At 16 weeks, after confirming the degree of glucose intolerance, high-fat diet-fed rats were randomly subdivided into three groups (n = 6/group): untreated group (HF), treated with dapagliflozin 1 mg/kg/day (HFSG) and treated with metformin 30 mg/kg/day (HFM). The treatment was continued for 4 weeks. We observed that dapagliflozin or metformin mitigated the enhanced expression of renal gluconeogenic enzymes, PEPCK, G6Pase and FBPase, as well as improved glucose tolerance and renal function in obese rats. Dapagliflozin downregulated the elevated expression of gluconeogenic transcription factors p-GSK3β, p-CREB and coactivator PGC1α in the renal cortical tissue. Metformin reduced the expression levels of renal cortical FOXO1 and CREB. Furthermore, reduced renal insulin signaling was improved and renal oxidative stress was attenuated by either dapagliflozin or metformin treatment in obese rats. We concluded that glucose tolerance was improved by dapagliflozin in obese prediabetic rats by suppressing renal glucose release from not only glucose reabsorption but also renal gluconeogenesis through improving renal cortical insulin signaling and oxidative stress. The efficacy of dapagliflozin in improving renal insulin signaling, oxidative stress and renal function was greater than that of metformin.
Myat Theingi Swe, Laongdao Thongnak, Krit Jaikumkao, Anchalee Pongchaidecha, Varanuj Chatsudthipong and Anusorn Lungkaphin
Keerati Wanchai, Sakawdaurn Yasom, Wannipa Tunapong, Titikorn Chunchai, Parameth Thiennimitr, Chaiyavat Chaiyasut, Anchalee Pongchaidecha, Varanuj Chatsudthipong, Siriporn Chattipakorn, Nipon Chattipakorn and Anusorn Lungkaphin
Obesity is health issue worldwide, which can lead to kidney dysfunction. Prebiotics are non-digestible foods that have beneficial effects on health. This study aimed to investigate the effects of xylooligosaccharide (XOS) on renal function, renal organic anion transporter 3 (Oat3) and the mechanisms involved. High-fat diet was provided for 12 weeks in male Wistar rats. After that, the rats were divided into normal diet (ND); normal diet treated with XOS (NDX); high-fat diet (HF) and high-fat diet treated with XOS (HFX). XOS was given daily at a dose of 1000 mg for 12 weeks. At week 24, HF rats showed a significant increase in obesity and insulin resistance associated with podocyte injury, increased microalbuminuria, decreased creatinine clearance and impaired Oat3 function. These alterations were improved by XOS supplementation. Renal MDA level and the expression of AT1R, NOX4, p67phox, 4-HNE, phosphorylated PKCα and ERK1/2 were significantly decreased after XOS treatment. In addition, Nrf2-Keap1 pathway, SOD2 and GCLC expression as well as renal apoptosis were also significantly reduced by XOS. These data suggest that XOS could indirectly restore renal function and Oat3 function via the reduction of oxidative stress and apoptosis through the modulating of AT1R-PKCα-NOXs activation in obese insulin-resistant rats. These attenuations were instigated by the improvement of obesity, hyperlipidemia and insulin resistance.