Systemic prostaglandin E1 infusion and hepatic aminonitrogen to urea nitrogen conversion in patients with type 2 diabetes in poor metabolic control.

Amino acid catabolism and urea synthesis are increased in type 2 diabetes mellitus in poor metabolic control. In different catabolic conditions, prostaglandins (PGs) of the E series produced metabolic effects on nitrogen metabolism, decreasing urea formation. In 10 patients with type 2 diabetes in poor metabolic control, urea synthesis and amino acid to urea nitrogen exchange were measured in the basal state and during an alanine load (6 hours) with 2-hour superinfusion of a PGE1 analog (30 microg/h) or saline in random order. The urea synthesis rate was calculated as the sum of urinary urea excretion and urea accumulation in total body water (TBW); total nitrogen exchange was calculated as the difference between infused amino acid-nitrogen and urea appearance. Plasma alpha-aminonitrogen (alpha-amino-N) increased 100% in response to alanine, to a steady-state without differences in relation to PG superinfusion. The urea synthesis rate (mean +/- SD) was 34.0 +/- 11.4 mmol/h in the basal period and increased to 161.2 +/- 37.0 during alanine + saline and to 113.5 +/- 34.6 during alanine + PG (P < .001). Nitrogen exchange was negative at baseline (-25.0 +/- 9.0 mmol/h). It became moderately positive during alanine + saline (14.6 +/- 25.1) and far more positive during alanine + PG (53.5 +/- 21.4), with the difference due to reduced urea formation. The metabolic effects of PG were not related to differences in insulin and glucagon. We conclude that PGE1 slows the high rate of hepatic urea-N synthesis in poorly controlled type 2 diabetes. Such metabolic effects have therapeutic implications.