Protein and glycoprotein synthesis and secretion by the diabetic liver

Abstract

Protein and glycoprotein synthesis and secretion by isolated perfused livers and isolated hepatocytes from control and streptozotocin diabetic rats have been investigated. (3)H-Leucine and (14)C-glucosamine incorporation were used as markers for protein and glycoprotein synthesis and secretion. Total protein secretion was reduced by 50% in the perfusate (p < 0.001) and by 36% in hepatocytes (p < 0.05), but glycoprotein secretion was unchanged in both preparations from diabetic animals. These differences were not due to changes in the available pool sizes of the different labels. On liver fractionation, all membrane components from the liver of diabetic animals had lowered (3)H-leucine: (14)Cd-glucosamine ratios in relation to the control animals. This was caused by enhanced glucosamine incorporation in relation to that of leucine. It is suggested that whereas protein synthesis is decreased in acutely diabetic rats, the production of glycoproteins is normal and occurs by the same pathway as in control animals.

Lipoprotein secretion by isolated perfused livers from streptozotocin-diabetic rats

“…The lowered ratio of 3H-leucine:14C-glucosamine in lipoprotein from diabetic livers, suggests that there is increased glycosylation of apoproteins in diabetes (Table 4). Enhancement of the incorporation ofglucosamine into secretory proteins by the perfused diabetic liver has been described previously [7]. When incorporation of the radioactive labels was expressed as a percentage of the total secreted protein, there was an increase in the 14C-glucosamine content of HDL from diabetic rats.…”

“…We believe that these changes in incorporation are due to the diabetic state and are not secondary to alterations in the pool sizes ofleucine and glucosamine. The pool sizes have been measured in hepatocyte preparations and were found to be similar with respect to leucine but slightly increased for glucosamine in the diabetic animals [7].…”

“…Isolated liver perfusion was performed as described by Mortimore et al [8], published in detail [7]. The perfusate consisted of KrebsRinger bicarbonate (pH 7.4) containing glucose 4 mg/ml, streptomycin 0.1 mg/ml, penicillin 1000 ~t/ml, bovine serum albumin 30 g/l, a mixture of the naturally occurring amino-acids (excluding leucine) 0.1 mmol/l of each, and heparin 1 u/ml.…”

“…The parallel increase in both VLDL and HDL concentrations is of interest since there is usually an inverse relationship between these lipoproteins [5] and because the HDL particle is partially derived from the metabolism of VLDL [6]. We have previously shown that in the perfused liver from diabetic rats the incorporation of leucine into protein was decreased whilst that of glucosamine was unchanged or even enhanced [7]. We therefore wished to extend this work by examining the incorporation of these labels into the specific lipoproteins in the study of the hyperlipidaemia of experimental diabetes.…”

Effect of diabetes on the sugar nucleotides in several tissues of the rat

“…Among the glycoconjugates studied have been the capillary basement membranes, which have been found to thicken in many tissues in diabetes [1] and to show increased synthesis in the kidney [2][3][4]; glycosaminoglycans, for which abnormal synthesis [5][6][7] or reduced levels [8] have been reported; serum glycoproteins, several of which have been found in increased concentrations in diabetes [9]; and material believed to be glycoprotein in nature which has been observed in both dog and human hearts in diabetes [10,11]. Moreover, a distinction has been made between the unimpaired synthesis of glycoproteins by diabetic liver and its markedly reduced glycogen formation [12,13].…”