The double-edged effect of insulin on the neuronal cell death associated with hypoglycemia on the hippocampal slice culture.

It is well known that the central nervous system (CNS) is vulnerable to hypoglycemia and hyperglycemia. Insulin is indispensable for serum glucose control and diabetes patients are on the relative or absolute deficient state of insulin. The role of insulin on the CNS, however, has not been fully elucidated, yet. To reveal the role of insulin on the neuronal survival, we have used in vitro system of an organotypic hippocampal slice culture from rat, and examine the neuronal cell death at the various glucose concentrations in the presence or absence of insulin. When glucose concentrations is varied to 0, 1, 3, 5 and 30 mM in the incubation medium, the neuronal cell death was minimum at 5mM, and no neuronal survival was observed under 1mM on the CA1. On the dentate gyrus granule cells (DG), on the other hand, the significant neuronal survival was observed even as low as 1mM. In the presence of 1 nM concentration of insulin, the neuronal cell death curve showed the U-shape, and the minimum death point was 3-5mM glucose concentrations at the CA1. At the DG, insulin did not show the protective effect up to 48 hours culture regardless of glucose concentration. In the absence of glucose, insulin accelerated the neuronal cell death both in the CA1 and DG. We concluded that insulin has a double-edged effect on the neuronal cell death dependent on glucose concentration, and that the CA1 and the DG have a different sensitivity to insulin in terms of cell survival.