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 complications has not been studied in detail. This investigation focused on the relationship between red blood cell 2,3-diphosphoglycerate and diabetic neuropathy, by measuring motor nerve conduction velocity and sciatic nerve 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-diphosphoglycerate concentration and diabetic neuropathy was also examined. Untreated diabetic rats had significantly lower concentrations of red blood cell 2,3-diphosphoglycerate, higher concentrations of serum total cholesterol and triglyceride, as well as reduced motor nerve conduction velocity and sciatic nerve blood flow, compared to untreated normal rats. Niceritrol prevented these abnormalities without correcting hyperglycemia in diabetic rats, but had no effect on these parameters in normal rats. Red blood cell 2,3-diphosphoglycerate concentration and motor nerve conduction velocity showed a positive correlation with sciatic nerve blood flow and 2,3-diphosphoglycerate, respectively. These observations suggest that ischemia/hypoxia plays an important role in the development of diabetic neuropathy, and that niceritrol has a therapeutic effect on this condition by improving endoneurial ischemia/hypoxia.
Hotta
N
N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Nakamura
J
J
Kakuta
H
H
Fukasawa
H
H
Koh
N
N
Sakakibara
F
F
Mori
K
K
Sakamoto
N
N
D019794:2,3-Diphosphoglycerate; D000818:Animals; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000517:prevention & control*; D004163:Diphosphoglyceric Acids / Q000097:blood*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D009531:Niceritrol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012044:Regression Analysis; D012584:Sciatic Nerve / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D014280:Triglycerides / Q000097:blood
D004163:Diphosphoglyceric Acids; D000960:Hypolipidemic Agents; D014280:Triglycerides; D019794:2,3-Diphosphoglycerate; D002784:Cholesterol; D009531:Niceritrol