Effect of short- and long-term diabetes on carnitine and myo-inositol in rats.

1. The effect of short- (2 wk) and long-term (20 wk) streptozotocin diabetes was studied on urine, blood, liver, heart, brain, skeletal muscle, pancreas and kidney concentrations of acid-soluble carnitine and free myo-inositol. 2. Short-term diabetic rats excreted significantly higher concentrations of carnitine as well as myoinositol than normal rats. Blood carnitine and myo-inositol were not different between normal and diabetic rats. Diabetes caused a decrease in liver, brain and pancreatic carnitine, but not in heart, skeletal muscle and kidney. Myo-inositol concentration was decreased in liver, heart and kidney but not in brain, pancreas and skeletal muscle. 3. Long-term diabetic rats had higher urinary excretions of both carnitine and myo-inositol. Blood carnitine did not change; however, myo-inositol was higher in diabetic than in normal rats. Diabetes caused a significant increase in liver and a decrease in heart, brain, skeletal muscle and pancreatic content of carnitine; no difference in kidney carnitine was noted. Myo-inositol content was elevated only in liver of diabetic rats. 4. We suggest that carnitine and myo-inositol concentrations are influenced both by short- and long-term diabetes through changes in tissue metabolism.     

Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts.

Fibroblast cell lines, designated R- and W cells, were generated, respectively, from mouse embryos homozygous for a targeted disruption of the Igf1r gene, encoding the type 1 insulin-like growth factor receptor, and from their wild-type littermates. W cells grow normally in serum-free medium supplemented with various combinations of purified growth factors, while pre- and postcrisis R- cells cannot grow, as they are arrested before entering the S phase. R- cells are able to grow in 10% serum, albeit more slowly than W cells, and with all phases of the cell cycle being elongated. An activated Ha-ras expressed from a stably transfected plasmid is unable to overcome the inability of R- cells to grow in serum-free medium supplemented with purified clones. Nevertheless, even in the presence of serum, R- cells stably transfected with Ha-ras, alone or in combination with simian virus 40 large T antigen, fail to form colonies in soft agar. Reintroduction into R- cells (or their derivatives) of a plasmid expressing the human insulin-like growth factor I receptor RNA and protein restores their ability to grow with purified growth factors or in soft agar. The signaling pathways participating in cell growth and transformation are discussed on the basis of these results.     

Effect of temperature on the induction of interferons by endotoxin and virus

Postic, Bosko (University of Pittsburgh, Pittsburgh, Pa.), Catherine DeAngelis, Mary K. Breinig, and Monto Ho. Effect of temperature on the induction of interferons by endotoxin and virus. J. Bacteriol. 91:1277-1281. 1966.-The effect of ambient and body temperature on interferon formation in rabbits injected intravenously with virus differed from that seen after injection of endotoxin. Newcastle disease virus-induced interferon (VII) was elevated by increasing ambient temperature to 35 C, whereas cooling of the rabbit at 4 C resulted in low VII levels. Neither of these conditions affected the titers of endotoxin-induced interferon (EII). However, a significant enhancement of EII levels was found in sera of shorn rabbits, in which the body temperature was lower than in unshorn animals by 1.0 to 1.5 F and the pyrogenic response to endotoxin was less by about 2 F. This enhancement of EII by relatively low body temperatures was also in striking contrast to the reported enhancing effect of high body temperature of the rabbit on the lethal action of endotoxin. It is suggested that the temperature optimum for formation of EII is lower than for formation of VII.