The research team of Wei Rui/Hong Tianpei of the Third Hospital of Peking University published the research results of the regeneration mechanism of islet β cells online in Diabetologia

On November 4, 2022, the research team of Wei Rui, researcher and Professor Hong Tianpei of the Department of Endocrinology, Peking University Third Hospital, β α published "Pancreatic alpha cell glucagon–liver FGF21 axis regulates beta cell" online in Diabetologia, a top journal specializing in endocrinology and metabolism regeneration in a mouse model of type 2 diabetes"
.

Screenshot of the paper

Diabetes is a major disease
that endangers human health and life.
Restoring the total number of cells β functional islets is a potential hope for improving the long-term efficacy of diabetes (or even curing diabetes), so the study of β cell regeneration and its mechanism has always been a hot and difficult point
in the field of diabetes.

The Wei Rui/Hong Tianpei research team first reported in iScience in 2019 that glucagon receptor (GCGR) monoclonal antibody (mAb) blocking glucagon signaling can induce transdifferentiation of islet α cells to β cells in mice with type 1 diabetes with absolute deficiency of β cells, thereby promoting β cell regeneration
.
The findings of the study were validated
by the findings published in PNAS by Professor Holland's team at the University of Texas in 2021.

In 2022, the Wei Rui/Hong Tianpei research team reported in iScience that GCGR mAbs promote the regeneration of β cells in mice with type 2 diabetes who are relatively deficient in β cells by promoting the transdifferentiation of α cells to β cells and inducing the regeneration
of β cells derived from pancreatic stem cells.
However, the mechanism by which blocking glucagon-GCGR signaling leads to β cell regeneration is unclear
.

α cell glucagon-liver FGF21 axis plays a regulatory role in β cell regeneration

This article is part of a series of studies on β cell regeneration and its mechanism by Wei Rui/Hong Tianpei's research team, aiming to elucidate the mechanism
of GCGR blockade leading to β cell regeneration.
First, GCGR mAbs promoted islet cell regeneration
in a type 2 diabetes model (db/db mice and high-fat feeding + low-dose streptocin 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 phenotype 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 and compared with liver mRNA sequencing data, and fibroblast growth factor 21 (FGF21) was determined to be a potential mediator
.
Furthermore, FGF21 neutralizing antibody, systemic Fgf21 knockout, and hepatocyte-specific Fgf21 knockout were used to prove that liver-derived FGF21 not only participated in the regulation of isolated β cell phenotype by GCGR mAb, but also mediated the regeneration
of diabetic mouse β cells caused by GCGR mAb.
This study revealed a new mechanism of GCGR blockade to improve diabetes control and promote β cell regeneration, and found that the α cyte glucagon-liver FGF21 axis plays an important role in β cell regeneration in diabetic mice, providing a new perspective
for the further development of therapeutic strategies to promote β cell regeneration.

Diabetologia is the official journal of the European Diabetes Society (EASD) and is one of
the oldest and most influential professional journals on diabetes.
The Wei Rui/Hong Tianpei research team has long been committed to the research of islet regeneration and β cell function regulation, and has published more than 10 related papers in SCI journals such as Diabetologia, Metabolism, EBioMedicine, and iScience in the past three years
.

Cui Xiaona, a postdoctoral fellow in the Department of Endocrinology, and Feng Jin, a master's student, are the co-first authors of this paper, and Wei Rui and Hong Tianpei are co-corresponding authors
.
This paper was supported
by the National Natural Science Foundation of China and the Beijing Municipal Natural Science Foundation.

Series study link:

1.
https://doi.
org/10.
1016/j.
isci.
2019.
05.
030

2.
https://doi.
org/10.
1016/j.
isci.
2022.
104567

3.
https://doi.
org/10.
1007/s00125-022-05822-2