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Get a sneak peek at the latest research!
On November 4, 2022, Diabetologia, a top journal specializing in endocrinology and metabolism, published the latest results
of the research on the regeneration mechanism of islet β cells in the Department of Endocrinology of Peking University Third Hospital (Beijing Medical Third Hospital).
The paper is: α Pancreatic alpha cell glucagon–liver FGF21 axis regulates beta cell regeneration in a mouse model of type 2 β diabetes）
。 Cui Xiaona, a postdoctoral fellow in the Department of Endocrinology of the Third Hospital of Beijing Medical University, and Feng Jin, a master's student, are co-first authors, and researcher Wei Rui and Professor Hong Tianpei are co-corresponding authors
.
Full text link: https://doi.
org/10.
1007/s00125-022-05822-2
diabetes is a major disease that endangers human health and life, The absolute or relative insufficiency of the ability of pancreatic islets β cells to secrete insulin is the core pathophysiological link
in the development of diabetes.
Restoring functional β total number of cells is a potential hope for improving the long-term efficacy (or even curing diabetes) of diabetes, and β cell regeneration and its mechanism research has always been a hot and difficult point
in the field of diabetes.
In 2019, the research team of Prof.
Wei Rui/Prof.
Tianpei Hong first reported the glucagon receptor (GCGR) monoclonal antibody (mAb) in iScience in 2019 Blocking glucagon signaling induces transdifferentiation of islet α cells to β cells in type 1 diabetic mice with absolute deficiency of β cells, thereby promoting β cell regeneration[1].
In 2021, the conclusions of this study were verified by the results of the research published in PNAS by the team of Professor William L.
Holland of the University of Texas Southwestern Medical Center in the United States in 2021 [2].
。 In 2022
In 2022, the authors reported in iScience that GCGR mAbs can promote β cell regeneration by promoting the transdifferentiation of α cells to β cells and inducing the regeneration of β cells derived from pancreatic stem cells in mice with type 2 diabetes who are relatively deficient in β cells [3].
However, the mechanism by which blocking glucagon-GCGR signaling leads to β cell regeneration is unclear
.
of action of GCGR blockade leading to regeneration of pancreatic islet β cells.
First, GCGR mAbs promoted islet cell regeneration in two mouse models of type 2 diabetes (db/db mice and high-fat feeding + low-dose streptosin diabetic mice).
Secondly, plasma conditioned culture or co-culture with primary hepatocytes using mouse β cell lines and primary mouse islets found that there were regulators regulating the phenotypic characteristics of ex vivo β cells in the plasma or primary hepatocytes extracted from GCGR mAb treated mice
.
Subsequently, plasma cytokine profiles were analyzed by solid-phase antibody chip technology, compared with liver mRNA sequencing data, and verified by ELISA, Western blot and real-time quantitative RT-PCR, and fibroblast growth factor 21 (FGF21) was determined is a potential mediator
.
Furthermore, blockade experiments such as FGF21-specific neutralizing antibody, systemic Fgf21 knockout, and hepatocyte-specific Fgf21 knockout proved that liver-derived FGF21 not only participates in the regulation of GCGR mAb on the phenotypic characteristics of ex vivo β cells, but also mediates GCGR mAb-induced cell regeneration
in mice with type 2 diabetes β mellitus.
This study revealed a new mechanism of GCGR blockade to improve diabetes control and promote β cell regeneration, and found that the α cell glucagon-liver FGF21 axis plays an important regulatory role in β cell regeneration in mice with type 2 diabetes, which provides a new perspective
for the further development of therapeutic strategies to promote β cell regeneration.
Pattern diagram of islet α cellular glucagon-liver FGF21 axis in regulating β cell regeneration
The European Diabetes Association (EASD) is one of the most important international academic organizations in the field of diabetes, and as the official journal of EASD, Diabetologia is one of the
oldest and most influential professional journals on diabetes.
This paper was supported
by the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, and the China Postdoctoral Science Foundation.
Prof.
Wei Rui/Prof.
Tianpei Hong's research team has long been committed to the study
of islet regeneration and β cell function regulation.
In the past 3 years, he has published in Diabetologia (IF=10.
460), Metabolism (IF=13.
934), and Lancet More than 10 related papers have been published in SCI journals such as EBioMedicine (IF=11.
205) and Cell subjournal iScience (IF=6.
107
).
Easter egg: Researcher Wei Rui and Professor Hong Tianpei have been recruiting postdoctoral fellows for many years and welcome young talents to join
.
Contact: weirui@bjmu.
edu.
cn or tpho66@bjmu.
edu.
cn
.
Hong Tianbei
Director of the Department of Endocrinology, second-level professor, chief physician and doctoral supervisor of the Third Hospital of Beijing Medical University
Vice Chairman of the Endocrinology Branch of the Chinese Medical Association
Vice President of Endocrinology and Metabolism Physician Branch of Chinese Medical Doctor Association
Chairman of the Diabetes Branch of Beijing Medical Association (7th).
Chairman of the Endocrinology Branch of Beijing Medical Association (7th), etc
He serves as the deputy editor-in-chief
of 6 journals, including the Chinese Journal of Diabetes and the Chinese Journal of Endocrinology and MetabolismLead the formulation of the People's Republic of China health industry standard "Diabetes Screening and Diagnosis"
His main research interests are basic and clinical research on diabetes and stem cell differentiation
.He has been responsible for more than 20 national, provincial and ministerial scientific research projects, including 9 National Natural Science Foundation of China (7 general projects, 1 key project, 1 major research plan), 1 national key research and development plan, etc
.He has published more than 400 papers in Chinese core journals and more than 90 SCI papers in famous journals such as JAMA
He won the 2018 National Famous Doctor-Excellent Achievement Award, the 2016 Beijing Science and Technology Award and other awards
Wei Rui
Researcher of the Department of Endocrinology, doctoral supervisor and academic leader reserve candidate of the Third Hospital of Beijing Medical University
Member of the Youth Committee of the Endocrinology Branch of the Chinese Medical Association
Young Director of Metabolic Biology Branch of Chinese Biophysical Society
Member of the Youth Committee of the Diabetes Branch of Beijing Medical Association and other academic part-time jobs
Main research directions: islet regeneration and new targets for diabetes treatment
He is responsible for 7 projects of the National Natural Science Foundation of China, the National Key R&D Program, the Beijing Natural Science Foundation of China, and 9 other fund projects
He has published 46 academic papers as the first or corresponding author, including 26 papers in SCI journals such as Diabetologia, Metabolism, EBioMedicine, Trends in Endocrinology and Metabolism
.Obtained 2 national invention patents
Won the Beijing Science and Technology Award
China Insulin Secretion Research Rising Star Award and other awards
Where to see more endocrinology clinical knowledge? Come to the "doctor's station" and take a look 👇
References:
[1] Wei R,Gu L,Yang J,et al.
Antagonistic glucagon receptor antibody promotes alpha-cell proliferation and increases beta-cell mass in diabetic mice.
iScience,2019; 16:326-339.
https://doi.
org/10.
1016
/j.
isci.
2019.
05.
030
[2] Wang MY,Dean ED,Quittner-Strom E,et al.
Glucagon blockade restores functional beta-cell
mass in type 1 diabetic mice and enhances
function of human islets.
Proc Natl AcadSci USA.
2021; 118(9):e2022142118.
https://doi.
org
/10.
1073/pnas.
2022142118
[3] Cui X,Feng J,Wei T,et al.
Pro-α-cell-derived
β-cells contribute to β-cell neogenesis induced
by antagonistic glucagon receptor antibody in
type 2 diabeticmice.
iScience.
2022; 25(7):
104567.
https://doi.
org/10.
1016/j.
isci.
2022.
104567
The source of this article Medical Endocrinology Channel
Responsible editorTangerine
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