Protein and carbohydrate metabolism in metabolic acidosis
Chronic renal failure (CRF) is associated with loss of lean body mass, a high incidence of malnutrition, and with insulin resistance. CRF is often complicated by metabolic acidosis. Metabolic acidosis is known to alter both protein and carbohydrate metabolism. A series of studies have been undertaken to investigate the effect of metabolic acidosis on protein metabolism in both normal and CRF human subjects, and to study whether metabolic acidosis in CRF affects insulin sensitivity. Protein turnover was studied using the technique of primed constant infusions of L-[1-13C]leucine. Normal subjects were studied before and after ammonium chloride induced metabolic acidosis. Acidosis was associated with increased protein turnover and amino acid oxidation. In CRF subjects, correction of acidosis with sodium bicarbonate decreased protein turnover and amino acid oxidation. The effect of acidosis in CRF on insulin mediated carbohydrate metabolism was studied using the technique of the hyperinsulinaemic euglycaemic clamp. Insulin sensitivity increased with correction of acidosis. By combining L-[1-13C]leucine infusions with hyperinsulinaemic euglycaemic clamps, the response of protein metabolism to hyperinsulinaemia was measured before and after correction of acidosis. The presence of acidosis did not impair the ability of insulin to modulate protein metabolism. There is therefore, dissociation between the effects of acidosis in CRF on insulin mediated carbohydrate metabolism and insulin mediated protein metabolism. In summary, metabolic acidosis increases protein catabolism in both normal and CRF man and may contribute to the loss of lean body mass characteristic of CRF. Insulin resistance in CRF improves with correction of acidosis. However the effects of acidosis on protein metabolism are not mediated via alterations in insulin sensitivity.