Studies on peripheral nerve and lens in long-term experimental diabetes: effects of the aldose reductase inhibitor statil.
This study determined the axonal transport of choline acetyltransferase (ChAT) activity and its content in several tissues in nondiabetic control rats and in four groups of rats with streptozotocin-induced diabetes of 6-months duration. Diabetic rats were either untreated, treated only with either the aldose reductase inhibitor Statil (Imperial Chemical Industries, Pharmaceuticals Division, Macclesfield, UK) or insulin, or were given the two in combination. Insulin treatment consisted of a single weekly injection of a long-acting insulin, a regime designed not to control the diabetes, but to provide regular respite from the catabolic dominance of uncontrolled diabetes. Elevated levels of sugars and polyols in the sciatic nerves of untreated diabetic animals were markedly attenuated by Statil. The reduced myo-inositol content and reduced axonal transport of ChAT activity also seen in these nerves were prevented by Statil, but a reduced motor nerve conduction velocity was attenuated only by Statil and insulin in combination. The presence of cataracts in all diabetic animals was associated with hyperhydration of the lens. The level of hydration and presence of cataracts were reduced by Statil, particularly in combination with insulin. ChAT activities of the iris, adrenal gland, and superior cervical ganglion were similar in all groups. Skeletal muscles showed wasting while the ileum showed an increased weight per unit length in diabetic rats. These tissues also displayed alterations in ChAT activities, particularly when referenced to unit weight of tissue, which may have been a consequence of the weight changes rather than diabetes per se.(ABSTRACT TRUNCATED AT 250 WORDS)
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001370:Axonal Transport; D001835:Body Weight; D002241:Carbohydrates / Q000032:analysis; D002795:Choline O-Acetyltransferase / Q000032:analysis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D007082:Ileum / Q000032:analysis; D007294:Inositol / Q000032:analysis; D007908:Lens, Crystalline / Q000032:analysis*; D008297:Male; D009132:Muscles / Q000032:analysis; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000032:analysis* / Q000503:physiopathology; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000032:analysis; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D002241:Carbohydrates; D010793:Phthalazines; D011724:Pyridazines; C042829:ponalrestat; D007294:Inositol; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D002795:Choline O-Acetyltransferase