Form 3
Report for Joint/Usage Research Program for Endocrine/Metabolism(Fiscal Year 2022)
Date：2023/5/15

To Director of Institute for Molecular and Cellular Regulation, Gunma University
Principal Applicant
Institution

Beijing Tongren Hospital, Capital Medical University

Position

Professor

Name

Jinkui Yang

We report on the results of joint research in fiscal 2022 as below.
（Program No.

）

１．Research Title

Berberine promotes GLP-1 secretion through hERG potassium channel inen-teroendocrine L-cells.

２．Purpose andSignificance of theresearch project

Berberine (BBR), one kind of Chinese traditional medicine, has applications as adrug in treating type 2 diabetes mellitus and hyperlipidemia for hundreds ofyears. However, the mechanism is still unknown. This study is to explore thefunction of BBR on GLP-1 exocytosis and clarify the molecular mechanism ofBBR in enteroendocrine L-cells.

３．Period of The Program

April 1, 2022 ～ March 31, 2023

４．Project Members
NameAge

Sex

Affiliation

Position

Role（Principal Applicant）

Jinkui Yang

60

M

Hao Wang

41

M

Yingchao Yuan

29

F（Research Collaborators）

Endocrinology
depart- Position：Professorment, Beijing Tongren Degree：MD, PhDHospital, Capital Medical Acquisition date：
University
2003.10
Endocrinology lab, Beijing
Tongren Hospital, Capital
Medical University
Endocrinology
department, Beijing Tongren
Hospital, Capital MedicalUniversity

Associate professor

Experimental executor

Graduate student

Experimental executor※If additional space is required, please attach a separate sheet.
５．Collaborating Researcher Name ofIMCR
of IMCR
Laboratory

1 / 3

Project director

Name

Tetsuro Izumi

Institute for Molecular andCellular Regulation
IMCR
Gunma University

６． Research Plans
1. Generation of hERG intestinal epithelial cell specific null mice (hERG pVillin-cre).
2. Check blood glucose and serum insulin, GLP-1, GIP concentrations in control and hERG pVillin-cre
mice that underwent an oral glucose tolerance test after treatment with NS or BBR.
3. Detect GLP-1 secretion ability of NS or BBR treated intestinal epithelial cells that were stimulated withglucose plus forskolin and IBMX.
4. Detect GLP-1 secretion ability of NS or BBR treated Glutag cells (L cell line) that were stimulated withglucose plus forskolin and IBMX.

７．Research results:
1. Finishing generation of hERG-pVillin-cre mice.
2. BBR treated control mice showed relieved glucose tolerance and increased serum GLP-1 level compared with those of NS treated control mice.
3. BBR treated hERG pVillin-cre mice showed no effect on glucose tolerance and serum GLP-1 levelcompared with those of NS treated control mice.
4. BBR promoted GLP-1 secretion in intestinal epithelial cells.
5. BBR promoted GLP-1 secretion in L cells.

８．Present status of academic conference presentations and research papers associated with the resultsof the joint research, and exchange of information on the joint research with the collaborating researcher atIMCR.
(As much as possible, please state papers that include the names of the collaborating researcher at IMCR
or papers stating that the research was supported by the Joint Research Program with IMCR.
Regarding papers, please send a PDF file together with the report to the email address of the general affairs section of the Institute.) Office of General Affairs: kk-msomu4@jimu.gunma-u.ac.jp① Please list the publications that include the name of the collaborating researcher from IMCR and send a
reprint of each publication to IMCR.

(a) Zhao MM, Lu J, Li S, Wang H, Cao X, Li Q, Shi TT, Matsunaga K, Chen C, Huang H, Izumi T, Yang JK. Berberine is
an insulin secretagogue targeting the KCNH6 potassium channel. Nat Commun. 2021 Sep 23;12(1):5616.
(b) Wang Hao*, Yuan Ying-Chao, Chang Cong, Izumi Tetsuro, Wang Hong-Hui*, Yang Jin-Kui*. The Signaling Protein
GIV/Girdin Mediates the Nephrin-dependent Insulin Secretion of Pancreatic Islet β Cells in Response to High
Glucose. Journal of Biological Chemistry, 2023, doi: 10.1016/j.jbc.2023.103045.

② Please list the publications that include a description that the research was supported by the Joint
Research Program with IMCR and send a reprint of each publication to IMCR.

a)

Zhao MM, Lu J, Li S, Wang H, Cao X, Li Q, Shi TT, Matsunaga K, Chen C, Huang H, Izumi T, Yang JK. Berberine
is an insulin secretagogue targeting the KCNH6 potassium channel. Nat Commun. 2021 Sep 23;12(1):5616.

③

List up to 3 conferences (name of conference, date of conference, and title of the presentation).

The 4th international symposium of endocrinology and metabolism, 12th Nov, 2022, Berberine is an insulin
secretagogue targeting the KCNH6 potassium channel.

④Exchange of information exchange with collaborating researcher from IMCR (please list main points ofcommunication).

The institutional collaboration agreement between IMCR and Beijing Tongren Hospital was established in

2 / 3Institute for Molecular andCellular Regulation
IMCR
Gunma University

April, 2016. Applicant and Dr. Hao Wang at Prof. Izumi’s laboratory have started this project and obtained
promising results to support future collaboration.

3 / 3Institute for Molecular andCellular Regulation
IMCR
Gunma University