Disease relevance of FGF21

• This indicates a dual function of FGF21 that may reflect changes in FGFR isotype during progression of differentiated hepatoma cells [1].
• These data support the development of FGF-21 for the treatment of diabetes and other metabolic diseases [2].
• FGF-21 administration also led to significant improvements in lipoprotein profiles, including lowering of low-density lipoprotein cholesterol and raising of high-density lipoprotein cholesterol, beneficial changes in the circulating levels of several cardiovascular risk markers/factors, and the induction of a small but significant weight loss [2].

High impact information on FGF21

• In islets isolated from diabetic rodents, FGF-21 treatment increased islet insulin content and glucose-induced insulin secretion [3].
• 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].
• 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].
• 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].

Biological context of FGF21

• Moreover, chronic activation of the PPARgamma pathway in 3T3-L1 adipocytes with the PPARgamma agonist and anti-diabetic agent, rosiglitazone (BRL 49653), enhances FGF-21 action to induce tyrosine phosphorylation of FGF receptor-2 [4].

Anatomical context of FGF21

• Forced overexpression of FGF21 in hepatocytes by gene targeting had no apparent impact on normal liver development and compensatory response to injury [1].
• Here, we investigated the effects of FGF-21 in the pancreatic beta-cell [3].
• Here we describe the early signaling events triggered by FGF-21 treatment of 3T3-L1 adipocytes and reveal a functional interplay between FGF-21 and peroxisome proliferator-activated receptor gamma (PPARgamma) pathways that leads to a marked stimulation of glucose transport [4].

Associations of FGF21 with chemical compounds

• Strikingly, treatment of cells with FGF-21 and rosiglitazone in combination leads to a pronounced increase in expression of the GLUT1 glucose transporter and a marked synergy in stimulation of glucose transport [4].

Physical interactions of FGF21

• Both FGF19 and FGF21 bind to the betaKlotho-FGFR4 complex; however, only FGF19 signals efficiently through FGFR4 [5].

Analytical, diagnostic and therapeutic context of FGF21

• 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 [1].
• In situ hybridization analysis confirmed that in contrast to FGF1 and FGF2, expression of FGF21 mRNA was limited to hepatocytes [1].
• 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