Nature Metabolism Makes Further Progress! Li Pingping's team at the Chinese Academy of Medical Sciences revealed the mechanism of insulin receptor degradation in the liver

iNature

On December 14, 2021, Huang Zhifeng of Wenzhou Medical University, Li Pingping of Peking Union Medical College of the Chinese Academy of Medical Sciences and Ren Jun of Zhongshan Hospital affiliated to Fudan University published a research paper entitled "Paracrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects" online in the journal Nature Communications.
The study identified paracrine FGF4 as a potent antihyperglycemic FGF by performing parallel tests of FGFR1c in diabetic mice
.

Importantly, the study found that, like FGF1, paracrine FGF4 was also more effective
than endocrine FGF21 in lowering blood sugar.

In addition, the study found that paracrine FGF4 and FGF1 exert their superior glycemic control role by targeting skeletal muscle, which is rich in expression of FGFR1c but lacks β-klotho (KLB), an essential FGF21 coreceptor
.

Mechanologically, both FGF4 and FGF1 upregulate the surface abundance of GLUT4 cells in skeletal muscle in an AMPKα-dependent but non-insulin-dependent manner
.

Chronic treatment with rFGF4 improves insulin resistance, inhibits fat macrophage infiltration and inflammation
.

It is worth noting that unlike FGF1 (pan-FGFR ligand), FGF4 has a more limited FGFR1c binding specificity and has no significant effect on
food intake.

In summary, the strong anti-hyperglycemic and anti-inflammatory properties of FGF4 in this study demonstrate its potential application prospects in the treatment of T2D and related metabolic disorders (click to read
).

The content is [iNature]