Impaired renal response to a meat meal in insulin-dependent diabetes: role of glucagon and prostaglandins.

The renal response to 100 g/1.73 m2 protein load in the form of a meat meal was studied in 19 normal subjects and 35 normoalbuminuric insulin-dependent diabetic patients (IDDs) under conditions of sustained euglycemia. The area under the glomerular filtration rate (GFR) curve rose above base line by 1,904 ± 292 in normals and 502 ± 237 ml/1.73 m2 in IDDs (P < 0.01). The meat meal induced a greater increment in the area under the glucagon curve in normals (14,930 ± 186 pg · ml-1 · min-1) than in IDDs (7,227 ± 67, P < 0.01); similarly urinary excretion of prostaglandin E2 and 6-ketoprostaglandin F1α rose by 119 and 98%, respectively, in normals but only by 2% (P < 0.01 vs. normals) and 10% (P < 0.01 vs. normals) in IDDs. The fractional albumin clearance rose by 102 and 251% in normals and IDDs, respectively. In five normal subjects indomethacin administration abolished the GFR, glucagon, prostaglandin, and albuminurie response to meat ingestion. Glucagon replacement under indomethacin treatment failed to restore these responses. In five diabetic patients, selected for having a flat glucagon and GFR response to a meat meal, replacement of glucagon to postprandial levels increased urinary vasodilatory prostaglandins and restored a normal GFR response. Thus in normal subjects renal vasodilatory prostaglandins appear to be the final effector of the renal hemodynamic and albuminurie response to a meat meal. The prostaglandin increase is likely to be mediated under physiological conditions by a glucagon rise, which, however, has no effect per se on renal hemodynamics. Diabetic patients have, on average, an impaired renal hemodynamic response to a meat meal, which is due to a relative failure in glucagon rise and in turn in renal prostaglandin synthesis. Copyright © 1990 the American Physiological Society.