Diurnal Variation of Sitagliptin-Induced Pharmacological Effects in C57BL/6J Mice.

Chronopharmacology is the study of the varying responses of drugs to changes in biological timing and endogenous periodicities. The dipeptidyl peptidase-4 inhibitor sitagliptin is a globally prescribed anti-hyperglycemic drug. Although dipeptidyl peptidase-4 inhibitors are usually administered once, the specific intake time is generally not mentioned. Therefore, this study aimed at investigating the diurnal effects of sitagliptin-induced anti-hyperglycemia in high-fat diet (HFD)-induced obesity in mice. Five-week-old male C57BL/6J mice were fed normal (control) diet or HFD for 10 weeks. During the last 2 weeks, the mice were administered saline or sitagliptin (10 mg/kg, per os) in the light or dark phase, respectively. At the end of the experiment, the mice were euthanized after an 18 h fasting period, and plasma and tissue samples (liver, kidney, and epididymal white adipose tissues) were collected, or the oral glucose tolerance test was performed. Sitagliptin administration in the light phase significantly decreased plasma glucose levels, insulin levels, hepatic steatosis, and restored the glucose tolerance compared with the HFD group. In contrast, these parameters remained unchanged in the dark phase-treated mice. Our data therefore suggests that sitagliptin portrays definite chronopharmacology, which may provide valuable information on the importance of drug administration timing for maximum pharmacological effects.

Chronopharmacology of dapagliflozin-induced antihyperglycemic effects in C57BL/6J mice.

Chronopharmacology is the study of the varying responses of drugs to changes in biological timing and endogenous periodicities. The selective sodium-glucose cotransporter 2 inhibitor, dapagliflozin, is a globally prescribed antihyperglycemic drug. Although dapagliflozin is usually administered once a day, the specific intake time is generally not mentioned. Therefore, this study aimed at investigating the diurnal effects of dapagliflozin on high-fat diet (HFD)-induced obesity in mice. Five-week-old male C57BL/6J mice were fed a normal (control) diet or HFD for 10 weeks. During the last 2 weeks, the mice were administered olive oil/ethanol emulsion or dapagliflozin (1mg/kg, p.o.) in the light or dark phase. At the end of the experiment, the mice were euthanized after an 18h fasting period, and plasma and tissue samples (epididymal white adipose tissues, liver, and kidney) were collected. Dapagliflozin administration in the light phase significantly decreased plasma glucose levels, insulin levels, adipose adipokines, and decreased the size of adipocytes, compared with the HFD group. In contrast, these parameters remained unchanged in the mice treated during the dark phase. Our data therefore suggests that dapagliflozin portrays definite chronopharmacology, which may provide valuable information on the importance of drug administration timing for maximal pharmacological effects.