【DIABETOLOGIA】Wei Rui/Hong Tianpei team of the Third Hospital of Beijing Medical University discovered a new mechanism of cell regeneration β islets!

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Written by Lily

Summary: Recently, the research team of Professor Wei Rui / Professor Hong Tianpei of the Department of Endocrinology of Peking University Third Hospital published the latest research results, finding that the α cell glucagon-liver FGF21 axis plays an important regulatory role in the regeneration of β cells in mice with type 2 diabetes, revealing a new mechanism of glucagon receptor (GCGR) blockade to improve diabetes control and promote β cell regeneration, and providing a new perspective for the development of therapeutic strategies to promote β cell regeneration
。

As a common non-communicable chronic disease, the global prevalence of diabetes is rising, endangering human health and life
.
Diabetes originates from a dual-hormone (insulin and glucagon) disorder – glucagon, a hormone secreted from the cells of the pancreas α that exerts its physiological role
by binding to glucagon receptors (GCGRs).
The main target organ of glucagon is the liver, which promotes glycogenolysis and gluconeogenesis, thereby increasing blood sugar levels; Therefore, blockade of glucagon-GCGR signaling can be used as a hypoglycemic strategy
.
Antagonistic GCGR monoclonal antibodies (mAbs) have a strong hypoglycemic effect
in mouse models of type 1 diabetes and type 2 diabetes, as well as in diabetic patients.

Restoring the total number of cells β functional islets is a potential hope for improving the long-term efficacy (or even curing diabetes) of diabetes, so β cell regeneration and its mechanism research has always been a hot and difficult point
in the field of diabetes.
Previous studies have found that GCGR mAbs promote β cell regeneration in diabetic mice; However, the mechanism behind this regeneration is unclear
.

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

On November 4, 2022, the research team of Wei Rui, researcher Wei Rui / Professor Hong Tianpei of the Department of Endocrinology of Peking University Third Hospital, published β α"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).

This study elucidates a new mechanism by which glucagon receptor (GCGR) blockade improves diabetes control and promotes β cell regeneration, and provides a new perspective
for the development of therapeutic strategies to β cell regeneration.

https://link.
springer.
com/article/10.
1007/s00125-022-05822-2

This article is one of a series of studies on β cell regeneration and its mechanism by the research team of Prof.
Wei Rui/Prof.
Hong Tianpei, aiming to elucidate the mechanism
of GCGR blockade leading to β cell regeneration.
Previous studies have shown that the hepatic islet axis is involved in GCGR antagonism-induced α cell proliferation
.
The research team believes that the liver may also be involved in the regeneration of β cells; Therefore, the goal of this study is to identify liver factors induced by GCGR antagonism and elucidate their role
in β cell regeneration.

First, the researchers investigated the effect
of GCGR mAbs on β cell quality and function in two mouse models of type 2 diabetes.
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, hepatocyte-specific Fgf21 knockout and other blockades proved 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.

The findings suggest that GCGR mAbs not only improve hyperglycemia but also increase functional β cell mass in mouse models of type 2 diabetes, and that these effects are at least partially mediated by liver-derived FGF21
.
This study reveals a new mechanism
of β cell regeneration regulated by the α cyte glucagon-liver FGF21 axis in diabetic mice.

The Third Hospital of Beijing Medical University is the first and corresponding author of this study, Cui Xiaona, a postdoctoral fellow in the Department of Endocrinology, and Feng Jin, a master's student, are co-first authors, and Professor Wei Rui and Professor Hong Tianpei are co-corresponding authors
.

Resources:

https://link.
springer.
com/article/10.
1007/s00125-022-05822-2

style="white-space: normal;box-sizing: border-box;">Note: This article is intended to introduce the progress of medical research and cannot be used as a reference
for treatment options.
If you need health guidance, please go to a regular hospital
.