Insulin-like Growth factor-I In Combination Research Articles

Gut Mucosal Homeostasis and Cellular Mediators after Severe Thermal Trauma and the Effect of Insulin-Like Growth Factor-I in Combination with Insulin-Like Growth Factor Binding Protein-3

Increased small bowel epithelial cell apoptosis and decreased cell proliferation lead to impairment of gut mucosal integrity and function after thermal injury. Impairment of gut integrity is associated with increased bacterial translocation and incidence of sepsis. The purpose of this study was to determine whether IGF-I/IGF binding protein (IGFBP)-3 can improve small bowel homeostasis after injury and by which cellular mechanisms these changes occur and to identify changes in apoptosis-related genes after burn and the effect of bile acid on small bowel epithelial cell apoptosis after burn. Rats sustained a thermal injury and received saline or the IGF-I/IGFBP-3 complex. Serum and small intestine were taken at 1, 2, 5, and 7 d after injury and serum inflammatory cytokines and mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators were measured. Apoptosis-related gene expression and the bile acid pool were determined in separate experiments up to 6 h after burn. Gut epithelial cell apoptosis as well as apoptosis-related genes were increased after the thermal injury, whereas bile acid secretion was significantly decreased (P < 0.05). IGF-I/IGFBP-3 significantly improved villous height and cells per villous by decreasing small bowel epithelial cell apoptosis and increasing proliferation (P < 0.05). Decreased apoptosis was associated with decreased Fas, Fas-ligand, and TNF when compared with saline (P < 0.05). A severe thermal injury caused an up-regulation of apoptosis and apoptosis-related genes and down-regulation of bile acid secretion. IGF-I/IGFBP-3 decreases small bowel epithelial cell apoptosis through down-regulation of the Fas pathway, which improves gut mucosal integrity after a severe thermal injury.

Olfactory bulb organ culture is supported by combined insulin-like growth factor-I and basic fibroblast growth factor

A rat olfactory bulb serum-free organ culture system has been developed, using either E19 or day 1 post-natal bulbs. Whereas E19 bulbs were self-sufficient, combined insulin-like growth factor-I (IGF-I) (100 ng/ml) and basic fibroblast growth factor (FGF) (50 ng/ml) supported growth and differentiation of day 1PN bulbs over 6 days. Morphological evidence for viability and differentiation in culture were seen, similar to that occuring in vivo, including development of glomerular layer and maintenance of mitral and tufted and granule cells. Quantitative data derived using radio-labelled amino acid or glucose incorporation supported additive or synergistic effects of IGF-I and FGF. This olfactory bulb organ culture system offers the potential for further studies of brain growth, differentiation and function in vitro.