Catalyst for adult-onset diabetes decoded

Scientists have long been puzzled by the exact molecular causes of diabetes. What seem clears is that people suffering from the common type-2 form of the disease ¨C known as adult-onset diabetes ¨C have an increased need for insulin because their body cells are resistant to insulin and the hormone is absorbed less well than in healthy individuals. In many cases, the cells of the pancreas can compensate by producing more insulin. If this ability to compensate is lost after a certain period of time, biomedical scientists refer to this as decompensation. As a result, the body experiences an insulin deficiency, resulting in elevated blood sugar levels and the development of diabetes.

An international research team led by Markus Stoffel, professor at the Institute of Molecular Health Sciences, recently discovered a molecule that plays a central role in this decompensation. The molecule is a micro-RNA, a type of small molecule related in structure to that of the genetic material DNA, of which humans have about 700 different types. These molecules perform important functions in the regulation of processes inside the body¡¯s cells.

Molecule as a switchpoint

In studies of various strains of mice, the scientists found micro-RNA-7 (miR-7) in lower concentrations among those insulin-resistant, yet well compensating strains than in the insulin-resistant strains exhibiting poor compensation. The researchers also identified differing levels of miR-7 in tissue samples taken from deceased body donors. In experiments on mice altered to produce either more or less miR-7, the researchers were ultimately able to show that this micro-RNA is a causal driver of decompensation and resulting defects in insulin secretion.

The researchers discovered that miR-7 regulates a whole network of genes and proteins. ¡°It works like a switchpoint,¡± explains Mathieu Latreille, a post-doctoral fellow in Stoffel¡¯s group and lead author of the study. High concentrations of miR-7, on the one hand, inhibit the secretion of insulin from beta cells, which produce the hormone in the pancreas. On the other hand, at higher miR-7 levels, beta cells loose their identity ¨C they dedifferentiate, as scientists describe it. This further reduces the production of insulin.

Stoffel envisions several applications for this new knowledge; for example, miR-7 could serve as a biomarker for the early detection of diabetes. The researcher also believes it would be possible in the future to produce molecular miR-7 inhibitors that could be administered as a drug and which might, at the very least, delay the disease. Such micro-RNA inhibitors are already being tested in clinical trials for other diseases and the research group led by Stoffel has been developing these kinds of neutralising molecules for several years now.