Adult male Sprague-Dawley rats with streptozotocin-induced diabetes (6 to 8 wk duration), treated or untreated with insulin, were studied with two aims: (a) to ascertain whether protracted diabetes in the rat is associated with changes in circulating plasma protein levels analogous to those reported in human diabetic patients with clinical evidence of complications; (b) to evaluate the effects of experimental diabetes on the net cumulative biosynthesis of 10 specific plasma proteins by the isolated liver, perfused for 24 hr.
Samples of liver donor plasma and samples of perfusate were analyzed by single radial immunodiffusion or by rocket immunoelectrophoresis for albumin, α1-macroglobulin and the acute phase glycoproteins: fibrinogen, α1-acid glycoprotein (Darcy), α1, acid glycoprotein (Kawasaki), haptoglobin, α2-(acute phase) globulin, hemopexin, C3-complement and ceruloplasmin.
Diabetes (6 to 8 wk), untreated with insulin, resulted in significantly increased liver donor plasma levels of α1-acid glycoprotein (Darcy) and α1-acid glycoprotein (Kawasaki); plasma levels of hemopexin and of C3 decreased to 75% and 30% of normal, respectively. Insulin treatment of diabetic liver donors for 6 to 8 wk prevented the increase in α1-acid glycoprotein (Darcy) and α1-acid glycoprotein (Kawasaki) and minimized the decrease in C3 to 75% of normal.
Perfused livers from untreated diabetic rats (6 to 8 wk) showed slightly decreased cumulative synthesis and secretion of α1-acid glycoprotein (Darcy); however, synthesis of albumin was reduced to 35% of normal and that of eight glycoproteins ranged from 25% of normal and that of eight glycoproteins renged from 25% of normal (fibrinogen) to 12% of normal (C3). The striking in vitro induction of increased synthesis of acute-phase proteins by cortisol plus insulin in the isolated perfused normalliver was in contrast to the severely attenuated induction in perfused livers of untreated diabetic rats, which ranges from 50% of normal for α1-acid glycoprotein (Darcy) to 5% of normal (C3).
Severely negative perfusate nitrogen balance and impaired glucose utilization by perfused untreated diabetic livers contrasted with positive nitrogen balance and good glucose utilization of normal livers in response to insulin plus cortisol. The plasma protein synthetic capacity and the in vitro response to insulin plus cortisol of perfused livers from insulin-treated diabetic rats were normal for seven of the proteins but moderately decreased for albumin, haptoglobin and C3.(HEPATOLOGY 1990; 11:635-645.)