CAG reduces plasma glucose in KM mice by inhibiting glucose
uptake
To determine the glucose-decreasing effect of AST andCAG (Chemical structure were listed in Figure 1A), KM mice were
administrated with AST and CAG for ten days. Metformin
and Dapagliflozin were used as positive drugs, respectively. Compared
with the vehicle group, metformin and Dapagliflozin efficiently
decreased plasma glucose at each time point, and Dapagliflozin showed a
higher efficacy. AST could not show a significant effect on
reducing plasma glucose, while CAG showed a more substantial
hypoglycemic effect and accompanied by a backward shift of the blood
glucose absorption peak (Figure 1B), indicating that CAG could
decrease glucose absorption in mice. The area under the curve of plasma
glucose (AUC) further confirmed the glucose-decreasing effect
of CAG in mice, which was similar to metformin (Figure 1C).
There are two approaches for glucose-diminishing in mice, including
promoting the glucose uptake and mobilization or inhibiting glucose
absorption (Pandey et al., 2015). To
reveal the underlying possible pattern of the glucose-decreasing inCAG -treated mice, we performed glucose uptake assay in cells by
using the 2-(N -(7-nitrobenz-2-oxa-1,3-diazol-4-yl)
amino)-2-deoxyglucose (2-NBDG) labelling method. Dapagliflozin markedly
decreased glucose uptake by a decrease in the signal of the 2-NBDG
within cells, and an opposite effect was observed in metformin-treated
cells, which was in accordance with the previous studies
(Lu et al., 2018). As shown in Figure 2,
cells treated with CAG showed a similar pattern with that of
Dapagliflozin, which was a significant reduction of the 2-NBDG signal.
To be noted, metformin, Dapagliflozin, and CAG could all
enhance insulin sensitivity as judged by an increase in the signal of
the 2-NBDG in the combination group compared with groups in the absence
of insulin. These results suggested that CAG , similar to
Dapagliflozin, could inhibit glucose uptake.