Evidence for an augmented glucagon dependence of hepatic glucose production in cirrhosis of the liver.
The role of endogenous glucagon in maintaining hepatic glucose production after an overnight fast in patients with cirrhosis of the liver was studied with arterial-hepatic-venous catheterization and using somatostatin to suppress glucagon secretion. Arterial glucagon levels were elevated in eight cirrhotics to 290 +/- 90 pg/ml (SEM) compared to 100 +/- 10 pg/ml (P less than 0.02) in five normal controls, and they were lowered during administration of somatostatin (SRIF; 250 microgram/h) by a mean of 154 pg/ml and 39 pg/ml in cirrhotics and controls, respectively. Basal net splanchnic glucose production (NSGP) was similar in patients with and without cirrhosis (approximately 100 mg/min) but declined more markedly during 30 min of SRIF in cirrhotics to a net splanchnic uptake of glucose of 30 +/- 20 ml/min, as opposed to a fall of NSGP by 44 +/- 2 mg/min in controls (P less than 0.01). To assure that NSGP declined during SRIF infusion due to the fall of glucagon levels, SRIF was combined with a glucagon infusion at 150 ng/m2 . min in four cirrhotics and in five control subjects. Arterial glucagon levels were elevated to a mean of 650 pg/ml and 559 pg/ml in cirrhotics and controls, respectively. NSGP increased after 40 min of SRIF and glucagon replacement to 179 +/- 33 mg/min in cirrhotics and significantly more, to 412 +/- 68 mg/min, in controls (P less than 0.01). Thus, hepatic glucose production during basal and elevated glucagon levels suggested hepatic resistance to glucagon in cirrhosis. Nevertheless, endogenous glucagon played an augmented stimulatory role in maintaining glucose production in the normal range since there was an exaggerated fall of hepatic glucose output during glucagon suppression.
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D005934:Glucagon / Q000097:blood* / Q000494:pharmacology; D005947:Glucose / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose