DISTAL SPLENORENAL SHUNT AND INSULIN-SECRETION, PLASMA-GLUCAGON, AND GLUCOSE-HOMEOSTASIS IN CIRRHOSIS

Over the 1 st postoperative yr, distal splenorenal shunt (DSRS) in cirrhotic patients is followed by a reduction in portal perfusion resulting from a spontaneous opening of portal-systemic collaterals. This can influence plasma levels of insulin and glucagon. Fasting plasma glucose, insulin, C-peptide, and glucagon and their 5-h responses to a protein meal (which directly stimulates the hormone secretions) were measured before and 3 and 12 mo after DSRS in 10 cirrhotic patients. Hormone effectiveness and pancreatic alpha- and beta-cell sensitivities to ammonia (NH3), amino acids, and glucose were also calculated. Liver function and portal vein diameter were assessed before each study. Seven cirrhotic patients treated with injection sclerotherapy of esophageal varices served as a control group. Liver function did not deteriorate in either patient group. An increase in fasting glucagon (from 181 +/- 22 to 242 +/- 22 and 255 +/- 22 pg/ml, p = 0.02) and NH3 (from 57 +/- 8 to 84 +/- 11 and 97 +/- 14 mug/dl, p = 0.04) and a decrease in glucagon effectiveness (from 0.56 +/- 0.06 to 0.39 +/- 0.05 and 0.35 +/- 0.03, p = 0.047) and portal vein diameter (from 16.0 +/- 1.1 to 11 .3 +/- 0.8 and 9.4 +/- 0.6 min, p < 0.001) was found only in DSRS patients. The elevation in glucagon was correlated with that of NH3 at 3 mo (r = 0.83, p = 0.003) and with the reduction of portal vein diameter at 1 yr (r = -0.81,p = 0.005). In cirrhosis, DSRS does not influence insulin secretion or its plasma level and effectiveness. Conversely, it worsens fasting hyperglucagonemia and hormone effectiveness. Our results suggest that these phenomena may eventually be caused by enhanced portal-systemic shunting, which increases circulating NH3 and impairs proper hormone presentation to liver cells.