The Double-edged Effect of Insulin on the Neuronal Cell Death Associated with Hypoglycemia on the Hippocampal Slice Culture

Abstract

It is well known that the central nervous system (CNS) is vulnerable tohypoglycemia and hyperglycemia. Insulin is indispensable for serum glucose controland diabetes patients are on the relative or absolute deficient state of insulin. The roleof insulin on the CNS, however, has not been fully elucidated, yet. To reveal the roleof insulin on the neuronal survival, we have used in vitro system of an organotypichippocampal slice culture from rat, and examine the neuronal cell death at the variousglucose concentrations in the presence or absence of insulin. When glucoseconcentrations is varied to 0, 1, 3, 5 and 30mM in the incubation medium, the neuronalcell death was minimum at 5mM, and no neuronal survival was observed under 1mMon the CA1. On the dentate gyrus granule cells (DG), on the other hand, thesignificant neuronal survival was observed even as low as 1mM. In the presence of1nM concentration of insulin, the neuronal cell death curve showed the U-shape, andthe 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 glucoseconcentration. In the absence of glucose, insulin accelerated the neuronal cell deathboth in the CA1 and DG. We concluded that insulin has a double-edged effect on theneuronal cell death dependent on glucose concentration, and that the CA1 and the DGhave a different sensitivity to insulin in terms of cell survival

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