Disease relevance of Fgf21

• Importantly, FGF-21 did not induce mitogenicity, hypoglycemia, or weight gain at any dose tested in diabetic or healthy animals or when overexpressed in transgenic mice [1].
• This indicates a dual function of FGF21 that may reflect changes in FGFR isotype during progression of differentiated hepatoma cells [2].

High impact information on Fgf21

• Here we describe a potential novel therapeutic agent for this disease, FGF-21, which was discovered to be a potent regulator of glucose uptake in mouse 3T3-L1 and primary human adipocytes [1].
• Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways [3].
• No effect of FGF-21 was observed on islet cell proliferation [3].
• Islets and INS-1E cells treated with FGF-21 were partially protected from glucolipotoxicity and cytokine-induced apoptosis [3].
• In conclusion, preservation of beta-cell function and survival by FGF-21 may contribute to the beneficial effects of this protein on glucose homeostasis observed in diabetic animals [3].

Anatomical context of Fgf21

• FGF-21 mRNA was most abundantly expressed in the liver, and also expressed in the thymus at lower levels [4].
• Forced overexpression of FGF21 in hepatocytes by gene targeting had no apparent impact on normal liver development and compensatory response to injury [2].
• Here, we investigated the effects of FGF-21 in the pancreatic beta-cell [3].

Analytical, diagnostic and therapeutic context of Fgf21

• The expression of FGF-21 mRNA in mouse adult tissues was examined by Northern blotting analysis [4].
• We showed that similar to FGF1 and FGF2, FGF21 mRNA was upregulated in neoplastic and regenerating liver after partial hepatectomy (PH) and CCl(4) administration [2].
• In situ hybridization analysis confirmed that in contrast to FGF1 and FGF2, expression of FGF21 mRNA was limited to hepatocytes [2].
• Short-term treatment of normal or db/db mice with FGF-21 lowered plasma levels of insulin and improved glucose clearance compared with vehicle after oral glucose tolerance testing [3].
• Immunohistochemistry of pancreata from db/db mice showed a substantial increase in the intensity of insulin staining in islets from FGF-21-treated animals as well as a higher number of islets per pancreas section and of insulin-positive cells per islet compared with control [3].

References