SALK RESEARCHERS FIND A NEW ROUTE FOR REGULATING BLOOD SUGAR LEVELS INDEPENDENT OF INSULIN
New molecular pathway controls blood glucose, circumventing insulin resistance
https://newatlas.com/…/insulin-alternative-fgf1-diabetes/
Previously, the lab showed that injecting FGF1 dramatically lowered blood glucose in mice and that chronic FGF1 treatment relieved insulin resistance.
In the current work, the team showed that FGF1 suppresses lipolysis, as insulin does. Then they showed that FGF1 regulates the production of glucose in the liver, as insulin does but by the alternate pathway FGF1/PDE4 .
FGF1 and insulin control lipolysis by convergent pathways
https://doi.org/10.1016/j.cmet.2021.12.004
Inexorable increases in insulin resistance, lipolysis, and hepatic glucose production (HGP) are hallmarks of type 2 diabetes. Previously, we showed that peripheral delivery of exogenous fibroblast growth factor 1 (FGF1) has robust anti-diabetic effects mediated by the adipose FGF receptor (FGFR) 1. However, its mechanism of action is not known. Here, we report that FGF1 acutely lowers HGP by suppressing adipose lipolysis. On a molecular level, FGF1 inhibits the cAMP-protein kinase A axis by activating phosphodiesterase 4D (PDE4D), which separates it mechanistically from the inhibitory actions of insulin via PDE3B. We identify Ser44 as an FGF1-induced regulatory phosphorylation site in PDE4D that is modulated by the feed-fast cycle. These findings establish the FGF1/PDE4 pathway as an alternate regulator of the adipose-HGP axis and identify FGF1 as an unrecognized regulator of fatty acid homeostasis…
• FGF1-FGFR1 signaling suppresses adipose lipolysis to curb hepatic glucose production
• FGF1 suppresses lipolysis by inhibiting cAMP/PKA axis via PDE4D-S44 phosphorylation
• Overexpression of PDE4D in the adipose tissue of diabetic mice corrects hyperglycemia
• FGF1/PDE4D antilipolytic pathway is responsive to fed/fast states
newatlas.com
Insulin-alternative hormone could open new type of diabetes treatment
Insulin is known for regulating blood glucose levels, and issues with its production lead to diabetes. But now, scientists at the Salk Institute have identified another molecular pathway that regulates blood glucose, which could open up a brand new avenue for treating diabetes.
](Insulin-alternative hormone could open new type of diabetes treatment)