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: