The influence of insulin and sorbinil on myoinositol uptake in peripheral nerve from normal and diabetic rats and a neuroblastoma cell line (N1E-115).

The uptake of myo-inositol was investigated in femoral nerve fascicular preparations taken from control and streptozotocin-diabetic rats and in a clonal murine neuro-blastoma cell line (N1E-115), as a model of the neuronal component of the nerve preparation. Uptake was investigated in medium containing glucose, 5.6-25 mmol/l and inositol, 4 x 10(-5) mol/l. In the presence of glucose (25 mmol/l) myo-inositol uptake was decreased in nerve taken from streptozotocin-diabetic animals when compared to control (26.4 +/- 2.2 pmol/100 micrograms protein/2 h vs 55.1 +/- 2.4 pmol/100 micrograms protein/2 h, p less than 0.005). Uptake in both preparations was higher in the presence of insulin added during the uptake experiment (73.4 +/- 5.7 pmol/100 micrograms protein/2 h and 64.4 +/- 3.9 pmol/100 micrograms/2 h, respectively). Prior treatment of the animals with insulin or with the aldose reductase inhibitor, sorbinil also resulted in an increase in myo-inositol uptake in streptozotocin diabetic nerve preparations. In control nerve preparations and in N1E-115 cells raising the glucose concentration from 5.6 through 25 mmol/l was associated with decreased myo-inositol uptake, with an inhibitory constant (Ki) of 21.4 mmol/l and 20.4 mmol/l for femoral nerve and N1E-115 cells respectively. An increase in myo-inositol uptake was found in N1E-115 cells, following pre-treatment of cells in culture with sorbinil or inclusion of insulin during the uptake experiment. Altered myoinositol metabolism may play a role in the functional and structural changes characterizing diabetic neuropathy. The effects of hyperglycaemia on myo-inositol uptake in experimental diabetes may be modified by insulin or by inhibition of sorbitol accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)