Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways

Fibroblast growth factor-21 (FGF-21) is a recently discovered metabolic regulator. Here, we investigated the effects of FGF-21 in the pancreatic beta-cell. In rat islets and INS-1E cells, FGF-21 activated extracellular signal-regulated kinase 1/2 and Akt signaling pathways. In islets isolated from healthy rats, FGF-21 increased insulin mRNA and protein levels but did not potentiate glucose-induced insulin secretion. Islets and INS-1E cells treated with FGF-21 were partially protected from glucolipotoxicity and cytokine-induced apoptosis. In islets isolated from diabetic rodents, FGF-21 treatment increased islet insulin content and glucose-induced insulin secretion. 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. Constant infusion of FGF-21 for 8 weeks in db/db mice nearly normalized fed blood glucose levels and increased plasma insulin levels. 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. No effect of FGF-21 was observed on islet cell proliferation. 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.     

Medical and morbidity surveillance findings among employees potentially exposed to TCDD

Available medical and morbidity surveillance findings from 1976 to 1978 for two employee cohorts potentially exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were compared with those of matched unexposed employees. The medical surveillance findings were derived from a screening programme offered to all active employees and included an analysis of various medical history questions and blood chemistry results. Group medical insurance claims served as the source of morbidity surveillance data and the period prevalence of selected diseases was analysed. Few significant differences between the exposed and unexposed were detected. Among the cohort of employees potentially exposed during the manufacture of 2,4,5-trichlorophenoxyacetic acid (2,4,5,-T), a significantly greater frequency of x-ray proved ulcer was reported and significantly more members of this group had diseases of the digestive system diagnosed. Such findings were absent in the more highly TCDD-exposed cohort engaged in 2,4,5-trichlorophenol production, making it unlikely that dioxin was a cause.