Diabetes-induced alterations in liver protein synthesis. Changes in the relative abundance of mRNAs for albumin and other plasma proteins.

Abstract

Mechanisms responsible for diabetes-induced alterations in liver protein synthesis were investigated in vivo and in perfused liver using Bio-Breeding Worcester (BB/W) control rats, spontaneously diabetic BB/W rats maintained on insulin therapy, and diabetic BB/W rats withdrawn from insulin therapy for 48 h. Withdrawal of insulin therapy in the diabetic rats resulted in marked alterations in a number of parameters related to liver protein synthesis compared to BB/W control or insulin-maintained diabetic rats. Alterations seen in vivo following withdrawal of insulin included changes in the relative concentrations of several plasma proteins, a 40% reduction in total liver RNA relative to DNA, a 5-fold reduction in albumin synthesis relative to the synthesis of total liver proteins, a 5-fold reduction in albumin mRNA relative to total RNA, reductions in the relative abundance of mRNAs for at least four plasma proteins other than albumin, and a relative increase in mRNA for at least one plasma protein. Alterations observed in perfused liver included reductions in total liver protein synthesis (60% of control), albumin production (24% of control), and total secretory protein production (44% of control). All parameters studied were essentially unchanged from BB/W control values when the diabetic rats were maintained on insulin therapy. The results indicate that insulin deficiency leads to marked reductions in liver protein synthesis, particularly the synthesis of albumin and other plasma proteins. The mechanisms responsible for these alterations include changes in the relative abundance of specific mRNAs and a decrease in total cellular RNA.