Correlation of albumin production rates and albumin mRNA levels in livers of normal, diabetic, and insulin-treated diabetic rats.

Abstract

We have studied the effects of alioxan-induced diabetes and subsequent insulin replacement on albumin and total hepatic protein synthesis. Diabetes resulted in a reduction to approximately 20% of normal in albumin synthesis relative to the rate of total protein synthesis in vivo and a reduction to 10% in the absolute rate of albumin secretion by perfused livers. In contrast, the synthesis of total secretory protein and retained hepatic protein was affected to a lesser extent by diabetes.Treatment of diabetic rats with insulin restored rates of albumin and total hepatic protein synthesis to normal levels. The molecular basis of these alterations in albumin synthesis was investigated by examining albumin mRNA levels in livers of normal, diabetic, and insulin-treated diabetic animals. The level of albumin mRNA, whether assayed by cell-free translation or by hybridization to a specific complementary DNA probe, was markedly decreased in livers of diabetic animals and was restored to normal by insulin treatment. These changes occurred in parallel with changes in the rates of albumin secretion observed in perfused liver, suggesting that albumin mRNA content is the primary factor responsible for altering rates of albumin synthesis under these conditions.A role for insulin in regulating protein synthesis in liver has not been clearly established. In rats, experimentally induced diabetes caused no change in liver protein synthesis rates in vivo, while synthesis rates in skeletal muscle and heart were markedly impaired (1). These findings are supported by studies using perfused tissues from normal rats in which measurements of protein synthesis showed that addition of insulin had no effect on the synthesis of hepatic proteins (2) but stimulated the synthesis of skeletal muscle (3) and heart (4) proteins. While some workers have reported that insulin stimulates liver protein synthesis (5), rates of protein synthesis were not determined rigorously in these experiments.Studies of protein synthesis in liver are complicated by the fact that this tissue synthesizes both proteins for export and intracellular proteins. The studies mentioned above measured primarily the synthesis of intracellular proteins. Other studies with perfused livers (6) or isolated hepatocytes (7) indicated an impaired secretion of proteins in diabetic rats. Such a defect may relate to the marked disruption and disorganization of the rough endoplasmic reticulum observed in liver of diabetic rats (8-10), as export proteins are synthesized almost exclusively on the rough endoplasmic reticulum (11).In the studies presented here, we have investigated the effect of alloxan-induced diabetes and subsequent insulin replacement on albumin and total protein production in vivo and in perfused livers, and have correlated the observed changes in albumin synthesis with changes in albumin mRNA levels. Diabetes resulted in a marked decrease in albumin synthesis and secretion in vivo and in perfused livers, with a corresponding decrease in the albumin mRNA level. T...

Medium-Chain Triacylglycerol Suppresses the Decrease of Plasma Albumin Level through the Insulin-Akt-mTOR Pathway in the Livers of Malnourished Rats

“…3). On the other hand, previous studies showed that albumin mRNA concentration and albumin synthesis are increased by insulin (35)(36)(37)(38). Therefore, the albumin improvement effect by dietary MCT may also be attributable to direct albumin mRNA expression through increased plasma insulin concentration.…”

Modulation of proinsulin messenger RNA after partial pancreatectomy in rats. Relationships to glucose homeostasis.

“…A correlation has been shown in rats between pancreatic proinsulin mRNA concentration and rates of in vivo incorporation of [3Hjleucine into proinsulin, showing comparable ability to assess rates of insulin biosynthesis (16,17). A correlation between tissue mRNA levels and protein synthetic rates also has been shown for other protein systems in vitro (23,24) and in vivo (25,26).…”

Metabolic differences in hepatocytes of obese and lean pigs

“…Albumin synthesis Albumin is synthesized in liver and represents from 12% to 18% of the total protein synthesized by the liver in rat hepatocytes (Peavy et al, 1978). Increased albumin synthesis was found in Iberian compared with Landrace hepatocytes (58%, P < 0.05; Figure 3b).…”