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dc.contributor.authorKrit Jaikumkaoen_US
dc.contributor.authorSasivimon Promsanen_US
dc.contributor.authorLaongdao Thongnaken_US
dc.contributor.authorMyat T. Sween_US
dc.contributor.authorMonruedee Tapanyaen_US
dc.contributor.authorKhin T. Htunen_US
dc.contributor.authorSuchart Kothanen_US
dc.contributor.authorNuttawadee Intachaien_US
dc.contributor.authorAnusorn Lungkaphinen_US
dc.description.abstractChronic consumption of a high-fat diet induces obesity and impairs the ultra-structure of organs and tissues. We examined the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor-dapagliflozin on renal and pancreatic injuries in obese condition. Rats were fed a high-fat diet for 16 weeks to induce obesity. After that, dapagliflozin or vildagliptin, 1.0 or 3.0 mg/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-fat diet-induced obese rats were elucidated. High-fat-diet 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-insulin resistant and glucose intolerance conditions. Also, high-fat-diet 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.en_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleDapagliflozin ameliorates pancreatic injury and activates kidney autophagy by modulating the AMPK/mTOR signaling pathway in obese ratsen_US
article.title.sourcetitleJournal of Cellular Physiologyen_US
article.volume236en_US Mai Universityen_US of Medicine 2en_US
Appears in Collections:CMUL: Journal Articles

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