Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic 
regulator expressed in multiple tissues including liver and adipose tissue. 
Although highest levels of expression are in pancreas, little is known about the 
function of FGF21 in this tissue. In order to understand the physiology of FGF21 
in the pancreas, we analyzed its expression and regulation in both acinar and 
islet tissues. We found that acinar tissue express 20-fold higher levels than 
that observed in islets. We also observed that pancreatic FGF21 is nutritionally 
regulated; a marked reduction in FGF21 expression was noted with fasting while 
obesity is associated with 3-4 fold higher expression. Acinar and islet cells 
are targets of FGF21, which when systemically administered, leads to 
phosphorylation of the downstream target ERK 1/2 in about half of acinar cells 
and a small subset of islet cells. Chronic, systemic FGF21 infusion 
down-regulates its own expression in the pancreas. Mice lacking FGF21 develop 
significant islet hyperplasia and periductal lymphocytic inflammation when fed 
with a high fat obesogenic diet. Inflammatory infiltrates consist of TCRb+ Thy1+ 
T lymphocytes with increased levels of Foxp3+ regulatory T cells. Increased 
levels of inflammatory cells were coupled with elevated expression of cytokines 
such as TNFα, IFNγ and IL1β. We conclude that FGF21 acts to limit islet 
hyperplasia and may also prevent pancreatic inflammation.