Huanglian-Renshen-Decoction (HRD) is widely used to treat
type 2 diabetes mellitus (T2DM) in China. However, the underlying mechanism is unclear. We aimed to investigate the mechanism by which HRD regulates the
glucose level. Forty 7-8-week-old db/db (BSK) mice were randomly assigned to the following four groups: model, low dose HRD (LHRD), high dose HRD (HHRD), and
saxagliptin (SAX). Additionally, 10 db/m mice were assigned to control group. The experimental mice were administered 3.03g/kg/d and 6.06g/kg/d of HRD in the LHRD and HHRD groups, respectively, and 10mg/kg/d
saxagliptin in the SAX group for 8 weeks. The control and model groups were supplied with distilled water. After the intervention, the pancreas and blood were collected and tested. Compared with that of model group, the fasting
blood glucose (FBG) was significantly decreased in all intervention groups (p < 0.05 or 0.01), whereas fasting serum
insulin (FINS) was increased significantly in both HHRD and SAX groups. The immunofluorescence images showed that the mass of insulin+ cells was increased and that of glucagon+ cells was reduced obviously in experimental groups compared to those of the model group. In addition, the coexpression of
insulin,
glucagon, and PDX1 was decreased in HHRD group, and the level of
caspase 12 in islet was decreased significantly in all intervention groups. However, little difference was found in the number and morphology of islet, and the expression of ki67, bcl2, bax,
caspase 3, and cleaved-
caspase 3 in the pancreas among groups. Interestingly, the cleaved-Notch1 level was increased and the Ngn3 level in islet was decreased significantly in HHRD group. The HRD showed dose-dependent effects on
glucose metabolism improvement through maintenance of β cell identity via a mechanism that might involve the Notch1/Ngn3 signal pathway in db/db mice.