Evidence for acute stimulation of fibrinogen production by glucagon in humans

Fibrinogen, an acute-phase protein, and glucagon, a stress hormone, are often elevated in many conditions of physical and metabolic stress, including uncontrolled diabetes.However, the possible mechanisms for this association are poorly known.We have studied the acute effects of selective hyperglucagonemia (raised from -200 to -350 pg/ml for 3 h) on fibrinogen fractional secretion rate (FSR) in eight normal subjects during infusion of somatostatin and replacement doses of insulin, glucagon, and growth hormone.Fibrinogen FSR was evaluated by precursor-product relationships using either Phe (n = 8) or Leu (« = 2) tracers.Hyperglucagonemia did not change either plasma Phe or Tyr specific activity.After hyperglucagonemia, fibrinogen FSR increased by -65% (from 12.9 ± 3.6 to 21.5 ± 6.1% per day, P < 0.025) using plasma Phe specific activity as the precursor pool.FSR increased by -80% (from 16.6 ± 4.8 to 29.4 ± 8.8% per day, P < 0.025) if plasma Phe specific activity was corrected for the ketoisocaproate/Leu enrichment (or specific activity) ratio to obtain an approximate estimate of intrahepatic Phe specific activity.FSR increased by -60% when using plasma Tyr specific activity as precursor pool (n = 8) (P < 0.05), as well as when using the Leu tracer precursorproduct relationship (n = 2).In conclusion, selective hyperglucagonemia for -3 h acutely stimulated fibrinogen FSR using a Phe tracer method.Thus, glucagon may be involved in the increase of fibrinogen concentration and FSR observed under stressed or pathologic conditions.Diabetes 46:1368-1371, 1997 F ibrinogen is an acute-phase protein (1) that is increased in uncontrolled diabetes, vascular disease, and smoking and in many conditions of physical and metabolic stress (2-6).Its plasma concentration has been recognized as a strong and independent cardiovascular risk factor (7). Nevertheless, the mechanisms and the factors that regulate fibrinogen synthesis in vivo are poorly understood.In humans, fibrinogen fractional secretion rate (FSR) was increased by acute insulin deficiency in IDDM (8), while it was decreased by short-term insulin infusion in both normal subjects and subjects with IDDM (8,9).