Synthesis and conversion of the renin precursor in vitro.
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Animals↗
Biomedical subjects
E Boel
Publications and source records attributed to E Boel.
In vitro studies on the conversion of the biosynthetic precursor of renin.
The initial translation product of mouse submaxillary gland mRNA has a molecular weight of about 50,000. We have now translated renin mRNA in frog oocytes which are known to be able to remove the so-called "pre"- or "signal"- sequence from products of injected mRNAs. From these injected oocytes, we could precipitate with antirenin a 48,000 dalton polypeptide. Treatment with kallikrein or trypsin of the oocyte product resulted in a decrease in amount of this 48,000 dalton protein and a corresponding increase in a 45,000 dalton protein, precipitable with antirenin. We conclude that the initial translation product of renin mRNA is a preprorenin of molecular weight 50,000, which in oocytes is enzymatically cleaved to render 48,000 dalton prorenin. Although kallikrein may be a physiological activator of renin, it appears to be not the only one since no mature, 40,000 dalton renin was formed.
Animals↗
Diabetic late complications: will aldose reductase inhibitors or inhibitors of advanced glycosylation endproduct formation hold promise?
Patients suffering from the severe complications associated with both insulin- (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM): nephropathy, retinopathy, neuropathy, and atherosclerosis are still largely left without a prospect of an efficient treatment. This is the case even if it has been assumed for decades and now finally proved by the results from the Diabetes Control and Complications Trial (DCCT) that hyperglycemia is the single main cause of these complications. Improved glycemic control as a result of intensive insulin treatment has the potential to reduce the incidence and progression of complications, but implementation and monitoring of improved glycemic control in all groups of IDDM and NIDDM patients in different communities will be difficult and expensive. Results from the recently terminated DCCT have shown that even with intensive insulin treatment, there will be a significant burden of complications on the diabetic population. It will, therefore, still be of immense importance for the long-term quality of life for the diabetic patient that additional possibilities are developed for prevention and intervention against diabetic complications. Almost two decades of research, animal model testing, and clinical trials have been conducted on various efficient aldose reductase inhibitors. Now the concept of inhibition of formation of advanced glycosylation endproducts on proteins and lipids resulting from extra- and intracellular hyperglycemia is entering the scene as an alternative or perhaps supplementary approach to reduce the occurrence of diabetic complications. An overview of the results from these two fields of research and associated drug-development programs will be presented along with thoughts on possible future developments.
Aldehyde Reductase↗