Objective
We investigated the effects of sodium‐glucose cotransporter 2 inhibitor, empagliflozin, and α‐glucosidase inhibitor, voglibose, on hepatic steatosis in an animal model of type 2 diabetes (T2DM).
Methods
Empagliflozin (OLETF‐EMPA) or voglibose (OLETF‐VOG) was administered to Otsuka Long‐Evans Tokushima fatty (OLETF) rats once daily for 12 weeks. Control Long‐Evans Tokushima Otsuka (LETO) and OLETF (OLETF‐C) rats received saline.
Results
Blood glucose levels were significantly suppressed in OLETF‐EMPA and OLETF‐VOG compared with the OLETF‐C group. The liver fat content was significantly higher in the OLETF‐C group than in the OLETF‐EMPA and OLETF‐VOG. Hepatic gene expressions involved in gluconeogenesis (glucose 6‐phosphatase [G6Pase], fructose‐1,6‐bisphosphatase [FBP1], and phosphoenolpyruvate carboxykinase [PEPCK]) and lipogenesis (acetyl‐CoA carboxylase [ACC], fatty acid synthase [FAS], and sterol regulatory element‐binding transcription factor 1c [SREBP‐1c]) were significantly decreased in the OLETF‐EMPA group compared with other OLETF groups (OLETF‐C and OLETF‐VOG). Sirtuin 1 (SIRT1) expression level and SIRT1 activity were markedly reduced in OLETF‐C rats; however, its expression increased in the OLETF‐EMPA and OLETF‐VOG. AMP‐activated protein kinase (AMPK) phosphorylation level was remarkably increased by empagliflozin treatment in OLETF rats compared with other OLETF groups. Long‐term empagliflozin and voglibose treatment reduced hepatic steatosis with suppression of gluconeogenesis and lipogenesis pathway in OLETF rats.
Conclusion
We suggest that this metabolic improvement might be related to SIRT1 and AMPK pathway in T2DM. But empagliflozin is thought to have more advantage to prevent hepatic steatosis than voglibose in T2DM.
The efficacy and biocompatibility of chitosan-alginate capsules were demonstrated in xenogeneic and allogeneic islet transplantations using small and large animal models of diabetes. This capsule might be a potential candidate applicable in the treatment of type 1 diabetes mellitus patients, and further studies in nonhuman primates are required.
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