BACKGROUND/AIMS: The aim of this study was to investigate glucagon and
insulin metabolism in order to clarify the mechanisms that lead to hy
perglucagonemia and hyperinsulinemia in cirrhosis. METHODOLOGY: Splanc
hnic output and metabolic clearance rates were studied in 16 cirrhotic
patients and 5 noncirrhotic controls. Splanchnic glucagon and insulin
output into the portal circulation were calculated by the difference
between portal venous and systemic arterial concentration multiplied b
y portal plasma flow. The metabolic clearance rate was calculated as t
he ratio of output to systemic arterial concentration. Portal blood fl
ow was measured by continuous local thermodilution. RESULTS: Arterial
glucagon levels were higher in cirrhotics than in controls. Glucagon o
utput was triple of that found in controls (52.4+/-7.0 vs 17.7+/-2.9 n
g/min, p<0.05). Both groups exhibited similar metabolic clearance rate
s of glucagon. Systemic arterial insulin values were higher in cirrhot
ics than in non-cirrhotics. Insulin output was not significantly diffe
rent between the two groups. However, metabolic clearance of insulin i
n cirrhotics was reduced to one half of the rate found in controls (23
7.0+/-39.8 vs. 450.5+/-17.5 mL/min, p<0.05). CONCLUSIONS: Hyperglucago
nemia in cirrhotic patients results from increased pancreatic output,
while hyperinsulinemia results from decreased insulin clearance.