Stem cell factor protects against neuronal apoptosis by activating AKT/ERK in diabetic mice

Neuronal apoptosis occurs in the diabetic brain due to insulin deficiency or insulin resistance, both of which reduce the expression of stem cell factor (SCF). We investigated the possible involvement of the activation of the MAPK/ERK and/or AKT pathways in neuroprotection by SCF in diabetes. Male C57/B6 mice (20-25 g) were randomly divided into four groups of 10 animals each. The morphology of the diabetic brain in mice treated or not with insulin or SCF was evaluated by H&E staining and TUNEL. SCF, ERK1/2 and AKT were measured by Western blotting. In diabetic mice treated with insulin or SCF, there was fewer structural change and apoptosis in the cortex compared to untreated mice. The apoptosis rate of the normal group, the diabetic group receiving vehicle, the diabetic group treated with insulin, and the diabetic group treated with SCF was 0.54 ± 0.077 percent, 2.83 ± 0.156 percent, 1.86 ± 0.094 percent, and 1.78 ± 0.095 percent (mean ± SEM), respectively. SCF expression was lower in the diabetic cortex than in the normal cortex; however, insulin increased the expression of SCF in the diabetic cortex. Furthermore, expression of phosphorylated ERK1/2 and AKT was decreased in the diabetic cortex compared to the normal cortex. However, insulin or SCF could activate the phosphorylation of ERK1/2 and AKT in the diabetic cortex. The results suggest that SCF may protect the brain from apoptosis in diabetes and that the mechanism of this protection may, at least in part, involve activation of the ERK1/2 and AKT pathways. These results provide insight into the mechanisms by which SCF and insulin exert their neuroprotective effects in the diabetic brain.

Hepatic iron status in Malaysians and Singaporeans.

Non-haemoglobin liver iron was estimated in 275 presumably normal individuals from Kuala Lumpur and Singapore at necropsy. Liver Iron concentrations were highest during the first two years after birth but declined sharply during childhood. They then rose gradually and reached a value of 20 mg/100gm in adult males. Liver iron concentrations of childbearing women remained low and it was only after menopause that values in women rose to those of males. Liver iron stores increased with age to a plateau of about 300 mg in adults, suggesting that this value may represent the adult size for liver iron store. Among the three major ethnic groups in Malaysia and Singapore, Chinese, being in a better socio-eonomic class, had larger liver iron stores. The median liver iron concentrations of Malaysians and Singaporeans, on the whole, were lower than those reported from western populations and as many as 35 per cent of the women were in a subclinical state of iron deficiency.