Effects of streptozotocin diabetes in the rat on blood levels of ten specific plasma proteins and on their net biosynthesis by the isolated perfused liver

Abstract

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, alpha 1-macroglobulin and the acute phase glycoproteins: fibrinogen, alpha 1-acid glycoprotein (Darcy), alpha 1-acid glycoprotein (Kawasaki), haptoglobin, alpha 2-(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 alpha 1-acid glycoprotein (Darcy) and alpha 1-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 alpha 1-acid glycoprotein (Darcy) and alpha 1-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 alpha 1-acid glycoprotein (Darcy); however, synthesis of albumin was reduced to 35% of normal and that of eight glycoproteins ranged 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 normal liver was in contrast to the severely attenuated induction in perfused livers of untreated diabetic rats, which ranges from 50% of normal for alpha 1-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.

Time-Dependent Plasma Protein Changes in Streptozotocin-Induced Diabetic Rats before and after Fungal Polysaccharide Treatments

“…It has been reported that the serum levels of α 1 -I III reduced in diabetes, while macroglobulin did not change appreciably in diabetic rats. , The serum Hp concentration in peritoneal dialysis patients with diabetes is lower than that in patients without diabetes, and it is not related to inflammation, nutrition, or adequacy of dialysis . Miller et al tried to elucidate whether protracted diabetes in rats is associated with changes in circulating plasma Hpx levels in rats analogues to those reported in human diabetic patients with clinical evidence of complications. The Vn might be increased from activated platelets in the early stage of diabetic nephropathy .…”

Dual Role of Insulin in Transcriptional Regulation of the Acute Phase Reactant Ceruloplasmin

“…In both alloxan-and streptozotocin-induced diabetic rats, the decrease in insulin level is accompanied by substantial reductions in plasma Cp (73)(74)(75), and treatment of diabetic rats with insulin restores plasma Cp to normal levels (75). Similarly, treatment of rats with streptozotocin decreases Cp synthesis by the isolated perfused liver, but is restored to normal after treatment of the rats with insulin (76). Taken together, these data suggest a possible regulatory activity of insulin on hepatic Cp synthesis and Cp plasma concentration in vivo.…”

Gender dimorphism in regulation of plasma proteins in streptozotocin-induced diabetic rats

“…Chen et al has reported upregulation of Hpx in plasma of human subjects with T1DM due to glucose‐induced oxidative stress. However, Miller et al demonstrated that the plasma level of Hpx in STZ‐induced diabetic rats was reduced to 75% that of normal rats. Hpx serves as the major vehicle for transportation of heme in the plasma by scavenging the heme released or lost due to turnover of heme proteins such as hemoglobin, thus protecting the body from oxidative damage induced by free heme .…”

“…Chen et al [8] has reported upregulation of Hpx in plasma of human subjects with T1DM due to glucose-induced oxidative stress. However, Miller et al [50] demonstrated that the plasma level of Hpx in STZ-induced A B Table 1.…”