In vitro inhibition of glucose phosphorylation by an aldose-reductase inhibitor (Tolrestat) in some non-insulin-sensitive rabbit tissues.
We have previously demonstrated that in some non-insulin-sensitive tissues (capillaries of eel swimbladder Rete mirabile, and rabbit eye choroidocapillary lamina, optic nerve, retina, and lens) glucose phosphorylation increases with the increase in the concentration of glucose, a characteristic relevant to the hyperglycemia of diabetes. In the present research we demonstrate an effect of the aldose reductase inhibitor, Tolrestat, on the glucose-phosphorylating activity of rabbit lens and optic nerve, by assaying the enzyme activity of tissue homogenates (in the presence of 10 mmol/L glucose) without or with 10 min preincubation with increasing concentrations of Tolrestat (2, 4, and 8 micromol/L). In the lens, a 18% inhibition (p < 0.01) was observed in the presence of 8 micromol/L Tolrestat. In the optic nerve, a 12% (p < 0.05) and a 21% (p < 0.01) reduction was recorded at 4 and 8 micromol/L Tolrestat, respectively. Significant inverse correlations existed between the concentration of Tolrestat and the phosphorylation rate of glucose of rabbit lens and optic nerve. The dose-dependent inhibition of glucose phosphorylation observed by us suggests that the inhibitory action of Tolrestat on glucose metabolism extends beyond the well-known effects of this compound on the polyol pathway, and might contribute to the refraining action of Tolrestat on the development and progression of late diabetic complications in non-insulin-sensitive tissues.
Iannello
S
S
Internal Medicine, University of Catania Medical School, Garibaldi Hospital, Italy.
Cavaleri
A
A
Camuto
M
M
Belfiore
F
F
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000378:metabolism*; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D009900:Optic Nerve / Q000378:metabolism*; D010766:Phosphorylation; D011817:Rabbits
D004791:Enzyme Inhibitors; D009281:Naphthalenes; C040550:tolrestat; D000449:Aldehyde Reductase; D005947:Glucose