Fig. 4.

Prospective chronotherapy for streptozocin (STZ). STZ is a cytotoxic agent used to treat pancreatic neuroendocrine tumors. STZ is actively transported into cells by the protein product of SLC2A2 and is associated with renal and hepatic toxicity. (A) The expression of Slc2a2 in mouse kidney and liver (1) is plotted as a function of circadian time. (B) Expression of SLC2A2 in human liver samples is plotted as a function of CYCLOPS phase. (C) Eleven-week-old male mice were dosed with STZ (green and purple) or saline (blue and red) at 7:00 AM (blue and green) or 7:00 PM (red and purple). Dosing time did not significantly impact the induction of hyperglycemia and expected treatment efficacy. (D) Body weight was used as a measure of gross toxicity. There was less weight loss among mice administered STZ at 7:00 PM.