Diabetes-induced alterations in the translational activity of specific messenger ribonucleic acids isolated from rat hearts.

Abstract

SUMMARY. During diabetes mellitus, total proteins and ribonucleic acids are significantly decreased in the rat heart, and these parameters can be increased by insulin administration. To determine whether all ribonucleic acids are equally sensitive to insulin, we examined the influence of this hormone on individual translatable ribonucleic acids. Cardiac ribonucleic acid prepared from control, untreated, and insulin-treated diabetic animals was translated in vitro in the presence of [ 3! S]methionine. The radiolabeled peptides were separated by two-dimensional gel electrophoresis and were analyzed by fluorometry. We found that diabetes induces both qualitative and quantitative changes in the predominance of a few specific translatable messenger ribonucleic acid species. The translation of 11 messenger ribonucleic acid species was significantly decreased and that of eight messenger ribonucleic acid species was significantly increased in diabetic preparations. Twelve of the 19 translation products were quantified by digital matrix photometry: three labeled peptides were observed only when cardiac ribonucleic acid from diabetic animals was added to the cell-free translation system, four new peptides appeared when cardiac ribonucleic acid from control animals was added, and although the remaining five peptides were translated in vitro after either control or diabetic ribonucleic acid was added, their relative predominance was altered 2-to 200-fold. When translation products coded for by messenger ribonucleic acids prepared from either diabetic or hypothyroid hearts were compared, we found that most of the alterations induced by diabetes were also induced by hypothyroidism. However, two of the 19 products were exclusively regulated by insulin, whereas two products unchanged in the diabetic heart were regulated exclusively by thyroid hormones. Thus, although each hormone specifically influenced the abundance of a few translatable messenger ribonucleic acids, most hormonesensitive translatable messenger ribonucleic acids are under the dual regulation of insulin and thyroid hormone. (Circ Res 57: 296-303, 1985)

Identification of multiple genes in bovine retinal pericytes altered by exposure to elevated levels of glucose by using mRNA differential display.

“…Although protein synthesis decreases with diabetes in most tissues (55)(56)(57), in retinal pericytes it increases (4) as do our clones encoding 27S and 28S ribosomal proteins. An autoimmune response against islet cells and insulin is important in the development of insulin-dependent diabetes mellitus (58,59).…”

Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans.

“…This alone could account for the failure to demonstrate significant changes in whole body estimates of protein synthesis during insulin deficiency. Other than in rat liver (23), a selective effect of insulin on protein synthesis has also been reported in rat cardiac muscle, where insulin deficiency was associated with a decreased transcription of 11 mRNA species and with a concomitant increased transcription of eight other specific mRNAs (76). Studies in humans using organ balance (16) and muscle biopsies (17,18) have failed to demonstrate an effect ofinsulin on whole muscle tissue protein synthesis.…”

Diabetes mellitus‐induced changes in the concentration of specific mRNAs and proteins

“…We found that diabetes induces both quantitative and qualitative changes in the predominance of few specific translatable mRNA species. 43 The translation of 11 mRNA species was significantly decreased and the level of 8 specific mRNAs was significantly increased in diabetic preparations. The relative predominance of these mRNAs were altered by 2-to 200-fold.…”