Objective:

2

To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β-cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine.

Methods:

2

The db/db mice were divided into the model (distilled water)

low-dose HRD (LHRD

3 g/kg)

high-dose HRD (HHRD

6 g/kg)

and liraglutide (400 μg/kg) groups using a random number table

8 mice in each group. The db/m mice were used as the control group (

n

=8

distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin

glucose

and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then

GLP-1

GLP-1R

prohormone convertase 1/3 (PC1/3)

PC2

v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA)

and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot

IHC

IF

and real-time quantitative polymerase chain reaction

respectivel

y.

Results:

2

HRD reduced the weight and blood glucose of the db/db mice

and improved insulin sensitivity at the same time (

P

<

0.05 or

P

<

0.01). HRD also promoted mice to secrete more insulin and less glucagon (

P

<

0.05 or

P

<

0.01). Moreover

it also increased the number of islet β cell and decreased islet α cell mass (

P

<

0.01). After HRD treatment

the levels of GLP-1

GLP-1R

PC1/3

PC2

MafA

and PDX1 in the pancreas and intestine significantly increased (

P

<

0.05 or

P

<

0.01).

Conclusion:

2

HRD can maintain the normal function and identity of islet β cell

and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.