Contributions of net hepatic glycogenolysis and gluconeogenesis to glucoseproduction in cirrhosis

Net hepatic glycogenolysis and gluconeogenesis were examined in normal (n = 4) and cirrhotic (n = 8) subjects using two independent methods [C-13 nucl ear magnetic resonance spectroscopy (NMR) and a (H2O)-H-2 method]. Rates of net hepatic glycogenolysis were calculated by the change in hepatic glycog en content before (similar to 11:00 PM) and after (similar to 7:00 AM) an o vernight fast using C-13 NMR and magnetic resonance imaging. Gluconeogenesi s was calculated as the difference between the rates of glucose production determined with an infusion of [6,6-H-2(2)]glucose and net hepatic glycogen olysis. In addition, the contribution of gluconeogenesis to glucose product ion was determined by the H-2 enrichment in C-5/C-2 of blood glucose after intake of (H2O)-H-2 (5 ml/kg body water). Plasma levels of total and free i nsulin-like growth factor I (IGF-I) and IGF-I binding proteins-1 and -3 wer e significantly decreased in the cirrhotic subjects (P < 0.01 vs, controls) . Postprandial hepatic glycogen concentrations were 34% lower in the cirrho tic subjects (P = 0.007). Rates of glucose production were similar between the cirrhotic and healthy subjects [9.0 +/- 0.9 and 10.0 +/- 0.8 mu mol kg body wt(-1) min(-1), respectively]. Net hepatic glycogenolysis was 3.5-fold lower in the cirrhotic subjects (P = 0.01) and accounted for only 13 +/- 6 % of glucose production compared with 40 +/- 10% (P = 0.03) in the control subjects. Gluconeogenesis was markedly increased in the cirrhotic subjects and accounted for 87 +/- 6% of glucose production vs. controls: 60 +/- 10% (P = 0.03). Gluconeogenesis in the cirrhotic subjects, as determined from t he 2H enrichment in glucose C-5/C-2, was also increased and accounted for 6 8 +/- 3% of glucose production compared with 54 +/- 2% (P = 0.02) in the co ntrol subjects. In conclusion, cirrhotic subjects have increased rates of g luconeogenesis and decreased rates of net hepatic glycogenolysis compared w ith control subjects. These alterations are Likely important contributing f actors to their altered carbohydrate metabolism.