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)
Dunlop
M E
ME
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Hill
M A
MA
Larkins
R G
RG
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005267:Femoral Nerve / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009447:Neuroblastoma / Q000378:metabolism*; D010693:Phloretin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D007093:Imidazoles; D048289:Imidazolidines; D007328:Insulin; D007294:Inositol; D000449:Aldehyde Reductase; C026411:sorbinil; D005947:Glucose; D010693:Phloretin