Decreased myo-inositol content and Na+-K+-ATPase activity in superior cervical ganglion of STZ-diabetic rat and prevention by aldose reductase inhibition.
Decreased sciatic nerve myo-inositol content and Na+-K+-ATPase activity have been associated with slowing of motor nerve conduction in the acutely diabetic rat and have been invoked as possible pathogenic factors in diabetic peripheral neuropathy. Aldose reductase inhibitors prevent these abnormalities in peripheral nerves of the streptozocin (STZ)-diabetic rat. Whether an analogous biochemical abnormality occurs in the autonomic nervous system and plays a role in the development of diabetic autonomic dysfunction is unknown. Therefore we examined the effect of 8 wk of untreated STZ diabetes and administration of 20 mg X kg-1 X day-1 of the aldose reductase inhibitor sorbinil on myo-inositol level and Na+-K+-ATPase activity in rat superior cervical ganglia. Both myo-inositol concentration and Na+-K+-ATPase activity were reduced in ganglia from untreated STZ-diabetic rats, and sorbinil administration prevented these abnormalities. Thus, a sorbinil-responsive metabolic defect involving myotional abnormalities in the somatic and autonomic nervous systems in diabetes.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D007093:Imidazoles; D048289:Imidazolidines; D007294:Inositol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase; C026411:sorbinil