For diabetes induction, C57BL/6 mice were fed with high fat diet (HFD) for 3 weeks (20% kcal protein, 20% kcal carbohydrate, and 60% kcal fat). Intraperitoneal administration of 60 mg/kg body weight streptozotocin (STZ, Sigma-Aldrich, St Louis, MO, USA) diluted in sodium citrate buffer was then performed for the following six days. Mice were fasted overnight prior to each STZ injection and blood glucose level measurement. Blood glucose level was evaluated using Accu-Check Integra (Roche Diagnostics, Shanghai, China). Mice with blood glucose level above 16.6 mM were assumed as diabetic mice, and were used for establishing diabetic HLI model as described previously.

For diabetes induction, C57BL/6 mice were given a high-fat diet for three weeks that contained 20% protein, 20% carbohydrate, and 60% fat. Sodium citratebuffer-diluted 60 mg/kg body weight streptozotocin (STZ; Sigma-Aldrich, St. Louis, MO) were administered intraperitoneally for the next constitutive six days. Prior to each STZ injection and blood glucose testusing Accu-Check Integra (Roche Diagnostics, Shanghai, China), mice were fasted overnight. Mice with blood glucose levels higher than 16.6 mM were considered diabetic and were utilized to establish the diabetic HLI model.

Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful.

BALB/c mouse are used as recipients and donors in the transplantation. Fifteen diabetic BALB/c mice were randomly divided into 5 groups (3 mice in each group). Then, 250 IEQ islets pretreated with or without bilirubin (20 uM) for 48 h were transplanted into the subrenal site of the diabetic mouse. Ferrin 1 (10 uM) and DFO (10 mM) pretreated islets were also transplanted for comparison. Following, the non-fasting glucose level and bodyweight was the mice were recorded daily.

Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful.

Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful.