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

Publication date: Available online 26 August 2019Source: Obesity Research & Clinical PracticeAuthor(s): Hiroki Yoshioka, Rurika Ohishi, Yui Hirose, Aya Torii-Goto, Sang Jun Park, Nobuhiko Miura, Masae YoshikawaAbstractChronopharmacology 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 (1 mg/kg, p.o.) in the light or dark phase. At the end of the experiment, the mice were euthanized after an 18 h 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 chronopharmacol...
Source: Obesity Research and Clinical Practice - Category: Eating Disorders & Weight Management Source Type: research