Development of fasting hyperglycemia in uremic rats

Rats which had been fasted for the previous 24 hr were subjected to either sham surgery, bilateral nephrectomy, or bilateral ureterotomy. The fast was continued for another 24 hr before the animals were decapitated and blood was obtained for determination of serum glucose, insulin, and urea nitrogen levels. A moderate but statistically significant (p < 0.02) fall in serum glucose levels occurred in rats made uremic by bilateral nephrectomy. In contrast, rats made equally uremic by bilateral ureterotomy developed a significant (p < 0.001) elevation of both serum glucose and insulin levels. The combination of hyperglycemia and hyperinsulinemia suggested that insulin resistance had developed in these rats, and this was confirmed by demonstrating that the hypoglycemic effect of exogenously administered insulin was attenuated in rats following bilateral ureterotomy as compared to sham-operated rats. Unilateral ureterotomy did not lead to the same metabolic response, and the difference in serum glucose levels between sham-operated and bilaterally ureterotomized rats disappeared when a 5% glucose solution was substituted for tap water as the rat's drinking water. It is suggested that the coexistence of fasting and metabolic acidosis led to increased renal gluconeogenesis in rats subjected to bilateral ureterotomy, and the combination of increased renal glucose production and insulin resistance was responsible for the development of fasting hyperglycemia.