Role of nitric oxide in deranged carbohydrate metabolism in chronic renal failure in wistar rats

ABSTRACT

Chronic renal failure is associated with a range of metabolic abnormalities that perturb glucose homeostasis. The present work was planned to investigate the glycemic effects of chronic renal failure in an attempt to explore the possible role of nitric oxide in these responses. Rats in this study were allocated into 6 groups 5/6 nephrectomy group for 2 weeks and its shamoperated control, 5/6 nephrectomy group for 4 weeks and its sham-operated control and L-arginine-treated 5/6 nephrectomy groups for 2 and 4 weeks. Plasma levels of creatinine, urea, glucose, insulin and nitrate as well as in vitro glucose uptake by diaphragm, following one hour of i.p. glucose load, were measured in all rats. The results showed significant increase in plasma glucose level and insulin/glucose ratio, significant decrease in glucose uptake by diaphragm and insignificant change in plasma insulin together with significant reduction in plasma nitrate level in 4 weeks 5/6 nephrectomy group, effects that were absent in 2 weeks 5/6 nephrectomy group. L-arginine-treated 4 weeks 5/6 nephrectomy group demonstrated significant elevation of nitrate level, significant decline in plasma creatinine and glucose levels and significant increase in glucose uptake by the diaphragm. In 5/6 nephrectomy rats and L-arginine-treated 5/6 nephrectomy rats, plasma nitrate level was inversely correlated with plasma creatinine and glucose and positively correlated with glucose uptake. It could be concluded that prolongation of chronic renal failure leads to impairment of nitric oxide [NO] bioavailability, associated with rise in plasma glucose and insulin resistance. Elevation of NO in uremia by L-arginine administration could improve glucose homeostasis by its beneficial effect on kidney function and stimulating glucose transport in muscle