Streptozotocin (stz)

Seventy-five rats were divided into five groups (15 rats in each group). The group of rats fed with a standard diet was referred to as normal control. The other rats were fasted 6–8 h prior to inducing diabetes. The diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight, Amresco, USA) followed by nicotinamide (120 mg/kg body weight, Sigma-Aldrich, Malaysia) in a 15-min interval. On the 7th day after the injection, the plasma glucose levels in rats were greater than 11.0 mmol/l and were confirmed, diabetic. The rats were maintained in this condition for 7 to 8 weeks. Then, the rats were treated for 30 days with quercetin, Metformin, and quercetin + Metformin. The plasma glucose levels in all rats were determined at the baseline and the end of the treatment period.

C57BL/6 mice were given STZ (Amresco, Solon, Ohio, USA) for a consecutive 5-day schedule (at 8∼12 a.m. every day) according to published methods and our previous protocol (Szkudelski, 2001 (link); Yu et al., 2016 (link)). Briefly, the compound was dissolved in a citrate buffer (pH 4.5), and injected intraperitoneally (60 mg/kg/d) within 15 min of dissolution. The control group received citrate buffer solution without STZ correspondingly. Three weeks post STZ stimulation, animals with random blood glucose value ≥300 mg/dL were defined as STZ-induced diabetic mice. The mice were then divided into three groups: (1) Control; (2) STZ; and (3) Metformin treated (STZ + Met), and housed in groups. The dose of Metformin administered to mice in this study was calculated according to clinically relevant human dose based on body surface area. Metformin (250 mg/kg/d; Sigma-Aldrich, St. Louis, MO, USA) dissolved in vehicle solution (5% sodium carboxymethylcellulose, CMC-Na; Sangon Biotech, Shanghai, China) was administered by gavage for 2 weeks (at 2∼4 p.m. every day). Mice in the Control and STZ groups were treated with vehicle correspondingly. On day 34, mice were used for ex vivo studies (Fig. 1A)

Animals were intraperitoneally injected with a single dose of STZ (Amresco, USA) at 60 mg/kg body weight, dissolved in 0.1 mM sodium citrate buffer (pH 4.5) [21 (link)]. On the fifth day after STZ administration, whole blood was obtained from the mice tail vein and glucose levels were measured using the blood glucose monitoring system (MAJOR, Taiwan). For the present study, hyperglycemia is defined as a blood glucose measurement of 20 mM or higher. Citrate buffer-treated mice were used as a normoglycemic control (blood glucose < 12 mM). The STZ-mice were randomly divided into 3 groups: hyperglycemic mice treated with vehicle and glibenclamide-treated mice (per day, 5 or 20 mg/kg, i.g, ×14 d) [11 (link),22 (link),23 (link)].