PLID scientists publish review on the making of insulin in health and diabetes

The discovery of insulin in 1921 has been one of greatest scientific achievements of the 20th century. Since then, the availability of insulin has shifted the focus of diabetes treatment from trying to keep patients alive to saving and improving the life of millions. Throughout this time, basic and clinical research has advanced our understanding of insulin synthesis and action, both in healthy and pathological conditions. Now, scientists of the Paul Langerhans Institute Dresden published a new review article on the making of insulin in a special issue of “Diabetologia”. It sheds light on the most recent findings on insulin synthesis and highlights their relevance in diabetes.

Diabetes mellitus affects millions of people worldwide and presents a growing issue and burden to the patients’ longevity and quality of life, as well as an increasing challenge to the healthcare systems. The perturbance of a highly sophisticated process, such as the insulin production, is key for the development of diabetes. Therefore, it is of great importance to understand how several environmental factors, including metabolic stress or inflammation, can hamper insulin production and lead to different forms of diabetes, depending on which step of the insulin supply chain is not working properly.

“In recent years the elucidation of each of these steps has progressed relentlessly: from the generation of the messenger RNA (mRNA) containing instructions for the biosynthesis of the insulin protein to the progressive intracellular maturation of the latter giving rise to the active insulin hormone”, explains Dr. Jovana Vasiljević, Postdoc in the Solimena lab of the Paul Langerhans Institute Dresden and first author of the review. “Yet, several aspects of this elaborate chain of events remain unclear. For instance, we still do not know how newly-synthesized insulin mRNA is transported from the beta cell nucleus to the cytosol, where its coded instructions are then translated for the assembly of the insulin protein. It is also unclear how this transport is regulated, where beta cells store the inactive insulin mRNA and how this inactive form is then either activated and recruited for insulin production, or degraded.”

“With our review, we tried to provide an overview of the key processes in insulin biosynthesis, including its post-transcriptional regulation and translation, prohormone conversion, packaging and maturation. Moreover, we discuss the currently known perturbations of these processes during the disease progression and pinpoint cell and molecular biological aspects that remain unclear. Although we continuously move forward in our understanding on how cells manufacture insulin, much remains to be uncovered regarding its production and release. However, I am nonetheless confident that ingenuity and access to ever new powerful methodologies will enable this knowledge gap to be filled in the future”, concludes Dr. Vasiljević.

Original Publication:

Vasiljević J, Torkko JM, Knoch KP, Solimena M. The making of insulin in health and disease.
Diabetologia. 2020 Oct;63(10):1981-1989. doi: 10.1007/s00125-020-05192-7. Epub 2020 Sep 7.

https://link.springer.com/article/10.1007/s00125-020-05192-7