All animal protocols were approved by Animal Care and Use Committee of the Affiliated Drum Tower Hospital of Nanjing University Medical School. C57bl/6 mice were obtained from Model Animal Research Center of Nanjing University. Male mice were randomly assigned into four groups and treated as follows: (a) control group (non‐diabetic mice without Streptozotocin (STZ)/ glycyrrhizin (Gly)/4‐phenylbutyrate (4‐PBA)), (b) STZ group (diabetic mice with STZ injection), (c) STZ + Gly group (STZ‐induced diabetic mice with Gly (Sigma‐Aldrich)) and (d) STZ + 4‐PBA group (STZ‐induced diabetic mice with 4‐PBA (Sigma‐Aldrich)). A model of STZ‐induced diabetic mice was established as previously described. 20 Briefly, mice were injected with STZ (40 mg/kg; Sigma‐Aldrich) for five consecutive days. When mice were considered as diabetes with blood glucose level > 13.9 mmol/L, some mice were treated with Gly (10 mg/kg/d) or 4‐PBA (50 mg/kg/d) one week after injection of STZ. Bodyweight and blood glucose level were measured every 4 weeks until the animals were killed.

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