Pancreatitis FGF21-deficient State Corrected By Replacement Therapy

[Pompadour]

This study looks interesting.

Pancreatitis is an FGF21-deficient state that is corrected by replacement therapy. - PubMed - NCBI

Abstract
The exocrine pancreas expresses the highest concentrations of fibroblast growth factor 21 (FGF21) in the body, where it maintains acinar cell proteostasis. Here, we showed in both mice and humans that acute and chronic pancreatitis is associated with a loss of FGF21 expression due to activation of the integrated stress response (ISR) pathway. Mechanistically, we found that activation of the ISR in cultured acinar cells and mouse pancreata induced the expression of ATF3, a transcriptional repressor that directly bound to specific sites on the Fgf21 promoter and resulted in loss of FGF21 expression. These ATF3 binding sites are conserved in the human FGF21 promoter. Consistent with the mouse studies, we also observed the reciprocal expression of ATF3 and FGF21 in the pancreata of human patients with pancreatitis. Using three different mouse models of pancreatitis, we showed that pharmacologic replacement of FGF21 mitigated the ISR and resolved pancreatitis. Likewise, inhibition of the ISR with an inhibitor of the PKR-like endoplasmic reticulum kinase (PERK) also restored FGF21 expression and alleviated pancreatitis. These findings highlight the importance of FGF21 in preserving exocrine pancreas function and suggest its therapeutic use for prevention and treatment of pancreatitis.

Unfortunatelly, i don't know biochemie and can't fully understand it . What can replacement therapy look like? What can be used for it?

 

[andrewkfletcher]

Metformin is being touted to correct FGF21. But this article says it can cause acute pancreatitis. I know metformin killed my Dad, he was never a diabetic, yet was given this drug as a preventative which I found very disturbing, yet Dad would not stop taking this medication and ultimately paid with his life. Metformin induced acute pancreatitis Thank you for your post, which led me to this article, which has now confirmed that metoformin caused Dad to develop pancreatitis, followed by pancreatic cancer and blocked bile duct.

 

[richofden]

This study looks interesting.

Pancreatitis is an FGF21-deficient state that is corrected by replacement therapy. - PubMed - NCBI

Abstract
The exocrine pancreas expresses the highest concentrations of fibroblast growth factor 21 (FGF21) in the body, where it maintains acinar cell proteostasis. Here, we showed in both mice and humans that acute and chronic pancreatitis is associated with a loss of FGF21 expression due to activation of the integrated stress response (ISR) pathway. Mechanistically, we found that activation of the ISR in cultured acinar cells and mouse pancreata induced the expression of ATF3, a transcriptional repressor that directly bound to specific sites on the Fgf21 promoter and resulted in loss of FGF21 expression. These ATF3 binding sites are conserved in the human FGF21 promoter. Consistent with the mouse studies, we also observed the reciprocal expression of ATF3 and FGF21 in the pancreata of human patients with pancreatitis. Using three different mouse models of pancreatitis, we showed that pharmacologic replacement of FGF21 mitigated the ISR and resolved pancreatitis. Likewise, inhibition of the ISR with an inhibitor of the PKR-like endoplasmic reticulum kinase (PERK) also restored FGF21 expression and alleviated pancreatitis. These findings highlight the importance of FGF21 in preserving exocrine pancreas function and suggest its therapeutic use for prevention and treatment of pancreatitis.

Unfortunatelly, i don't know biochemie and can't fully understand it . What can replacement therapy look like? What can be used for it?

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