Form 3
Report for Joint/Usage Research Program for Endocrine/Metabolism(Fiscal Year 2022)
Date：2023/5/17

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

College of Biology, Hunan University

Position

Associate Professor

Name

Honghui Wang

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

）

１．Research Title

Development of a Glucose-gated DNA-nanodevice for Glucose Control in Type I
and II Diabetes

２．Purpose andSignificance of theresearch projectThis project is the continuous study following a previous project. We aim to construct an intelligent therapeutic strategy to balance glucose homeostasis in bothType I and type II diabetes. In this study, we rationally design a glucose-responsive DNA-nanodevice capable of dynamically responding to diabetic
blood glucose levels and automatically promoting glucose uptake in the liver andskeletal muscle. Using this nanodevice, we have succeeded in restoring normal
blood glucose levels in both Type I and Type II diabetic mouse models.

３．Period of The Program

April 1, 2022 ～ March 31, 2023

４．Project Members
Name

Age

Sex

Affiliation

Position

Hunan University, College
of Biology

Position：Associate
Professor
Degree：PhD
Acquisition date：2010.3.31

Role（Principal Applicant）

Hong-Hui
Wang

42

M

Project director（Research Collaborators）

Hunan University, College
of Chemistry and ChemiGraduate student
cal Engineering
Hunan University, College
MeiXia Wang
25
F
Graduate studentof Biology
Hunan University, College
Jun Zhun
27
M
Graduate studentof Biology※If additional space is required, please attach a separate sheet.
５．Collaborating Researcher Name of
IMCR
Name
of IMCR
Laboratory
Fang He

26

F

1 / 4

Cell experiment
Animal experiments
Data analysis

Tetsuro Izumi

Institute for Molecular andCellular Regulation
IMCR
Gunma University

６． Research Plans① Investigate the role of glucose-gated nanodevice in regulating the dynamics of c-Met dimerization on
membrane and the GLUT4 translocation using TIRF microscope.
② We will study the glucose uptake using skeletal muscle organoids and liver organoids in the presenceof the glucose-gated DNA nanodevice.
③ We will carry out an intraperitoneal glucose tolerance test (IPGTT) to examine if glucose-gated DNA
nanodevice can regulate the hyperglycemia status in STZ mice mimicking Type I diabetes and db/db
mice mimicking Type II diabetes.

７．Research results:① We demonstrated that the glucose-gated DNA nanodevice is only activated when glucose levels rise
above 7 mM, subsequently triggering the c-Met/IRS2/AKT signaling pathway.

Figure 1. Distinct kinetic and phosphorylation patterns produced by insulin signaling stimulated by glucose-induced DNA-based nanodevices.
②

We showed that the glucose-gated DNA nanodevice can detect high glucose levels, prompting membrane translocation of GLUT4 at the single-cell level.

Figure 2. Glucose-responsive translocation of glucose transporter-4 (GLUT4) in hepatocytes equipped withthe glucose-gated DNA nanodevice (AS).

2 / 4

Institute for Molecular andCellular Regulation
IMCR
Gunma University

③

We characterized the ability of the glucose-gated DNA nanodevice to autonomously respond to highglucose levels (> 7 mM) and activate MET/AKT signaling and enhance the glucose uptake of skeletal
muscle organoids.

Figure 3. Autonomous glucose uptake in myotubes equipped with the glucose-gated DNA nanodevice forglucose homeostasis.

④ In our study involving STZ-induced Type I diabetic mice, we performed an intraperitoneal glucose

tolerance test. The results confirmed the glucose regulation function of glucose-gated DNA
nanodevices. We validated the capability of the nanodevice to significantly improve glucose tolerance
and prevent hypoglycemia.

Figure 4. Functionality of the glucose-gated nanodevice in regulating blood glucose in STZ-induced mice.

3 / 4Institute for Molecular andCellular Regulation
IMCR
Gunma University

⑤ Using Type II db/db diabetic mice, we performed an intraperitoneal glucose tolerance test. The results
confirmed the ability of the glucose-gated nanodevice to maintain glucose homeostasis. This approach effectively avoids hypoglycemia.

Figure 5. Efficacy of the glucose-gated nanodevice in regulating glucose in db/db diabetic mice.
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 at
IMCR.
(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.

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)
b)

③

Wu Yuchen, Huang Jin, He Hui, Wang Meixia, Yin Guanyu, Qi Lanlin, He Xiaoxiao*, Wang Hong-Hui*, Wang
Kemin*. Logic Nanodevice-Mediated Receptor Assembly for Nongenetic Regulation of Cell Behavior in Tumor-like Microenvironment. Nano Letters, 2023, 23(5):1801-1809.
Wang Meixia, Li Xiaoxiao, He Fang, Li Juan, Wang Hong-Hui*, Nie Zhou*. Advances in Designer DNA Nanorobots Enabling Programmable Functions. Chembiochem. 2022, e202200119. doi: 10.1002/cbic.202200119

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

None

④

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

The institutional collaboration agreement between IMCR and College of Biology Hunan university was established in April, 2016. Applicant and Dr. Hao Wang at Dr. Izumi’s laboratory have started this project andobtained promising results to support future collaboration.

4 / 4Institute for Molecular andCellular Regulation
IMCR
Gunma University