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We examined the effect of sodium\u2010glucose cotransporter 2 (SGLT2) inhibitor\u2010dapagliflozin on renal and pancreatic injuries in obese condition. Rats were fed a high\u2010fat diet for 16 weeks to induce obesity. After that, dapagliflozin or vildagliptin, 1.0 or 3.0\u2009mg\/kg\/day, respectively, was administered by oral gavage for 4 weeks. The effects of dapagliflozin on insulin resistance, kidney autophagy, pancreatic oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and apoptosis in high\u2010fat diet\u2010induced obese rats were elucidated. High\u2010fat\u2010diet fed rats demonstrated metabolic abnormalities including increased body weight, visceral fat weight, plasma insulin, plasma cholesterol, homeostasis model assessment (HOMA) index, and TAUCg, indicating the obese\u2010insulin resistant and glucose intolerance conditions. Also, high\u2010fat\u2010diet fed rats exhibited significant pancreatic injury accompanied by decreased kidney autophagy. Dapagliflozin or vildagliptin treatment for 4 weeks ameliorated pancreatic oxidative stress, ER stress, inflammation, and apoptosis and restored kidney autophagy in obese rats. Moreover, the morphology changes of the pancreas and kidney were improved in the treated groups. Interestingly, dapagliflozin showed higher efficacy than vildagliptin in improving body weight, visceral fat weight, plasma cholesterol level, and pancreatic oxidative stress in our model. Taken together, the present study demonstrated that the therapeutic effects of dapagliflozin attenuated pancreatic injury, pancreatic oxidative stress, ER stress, inflammation, apoptosis, and exerted renoprotective effects by restoring autophagic signaling in obese rats.<\/jats:p>","DOI":"10.1002\/jcp.30316","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T17:12:07Z","timestamp":1612977127000},"page":"6424-6440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Dapagliflozin ameliorates pancreatic injury and activates kidney autophagy by modulating the AMPK\/mTOR signaling pathway in obese rats"],"prefix":"10.1002","volume":"236","author":[{"given":"Krit","family":"Jaikumkao","sequence":"first","affiliation":[{"name":"Department of Radiologic Technology, Faculty of Associated Medical Sciences Chiang Mai University  Chiang Mai Thailand"},{"name":"Department of Radiologic 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