NICERITROL PREVENTS THE DECREASE IN RED-BLOOD-CELL 2,3-DIPHOSPHOGLYCERATE AND NEUROPATHY IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Nerve ischemia/hypoxia has been linked to the pathogenesis of diabetic complications. Red blood cell 2,3-diphosphoglycerate is an important regulator of peripheral tissue oxygenation; however, the relationship between 2,3-diphosphoglycerate concentration and diabetic complication s has not been studied in detail. This investigation focused on the re lationship between red blood cell 2,3-diphosphoglycerate and diabetic neuropathy, by measuring motor nerve conduction velocity and sciatic n erve blood flow in streptozotocin-induced diabetic rats. The effect of treatment with niceritrol, a nicotinic acid derivative that acts as a vasodilator and reduces serum lipid concentrations, on 2,3-diphosphog lycerate concentration and diabetic neuropathy was also examined. Untr eated diabetic rats had significantly lower concentrations of red bloo d fell 2,3-diphosphoglycerate, higher concentrations of serum total ch olesterol and triglyceride, as well as reduced motor nerve conduction velocity and sciatic nerve blood flow, compared to untreated normal ra ts. Niceritrol prevented these abnormalities without correcting hyperg lycemia in diabetic rats, but had no effect on these parameters in nor mal rats. Red blood cell 2,3-diphosphoglycerate concentration and moto r nerve conduction velocity showed a positive correlation with sciatic nerve blood flow and 2,3-diphosphoglycerate, respectively. These obse rvations suggest that ischemia/hypoxia plays an important role in the development of diabetic neuropathy, and that niceritrol has a therapeu tic effect on this condition by improving endoneurial ischemia/hypoxia .