A little over a decade ago, researchers reported the discovery of molecules central to the function of certain cells; microRNA. Since then, microRNA has been studied further, revealing more and more about its responsibilities within cells. The latest finding could be crucial in the fight against diabetes, one of many diseases plaguing today's population. MicroRNA or more specifically, miRNA-375, has been linked to the death of beta-cells in the pancreas.But firstly, a little background on diabetes. Type I diabetes is characterised by a loss of pancreatic beta-cells. These cells secrete the vital insulin hormone in the body. Insulin regulates the cellular uptake of glucose from the bloodstream thus maintaining blood-glucose levels. However, when beta-cells begin degenerating, so does the game of balance between glucose and insulin. Lacking insulin, the body's blood-glucose levels rise as cells are no longer instructed to absorb glucose. At this point, the affected person must develop a daily routine of insulin-replacement therapy, dietary management and ongoing monitoring. Not only does this routine interrupt one's life but any irregularity of it could lead to a number of complications including diabetic comas. All this, because of the death of a few microscopic units of life.
The newly discovered factor in the death of these units of life is miRNA-375. Researchers in Zurich found miRNA-375, a microRNA present in certain cells throughout the body, to be concentrated within beta-cells in the pancreas. The researchers, led by Markus Stoffel, Professor of Metabolic Disease at ETH Zurich, found that without miRNA-375 the beta-cells were unable to grow and consequently died. This was coupled with an increase in alpha-cells which are complementary to the beta-cells in the pancreas and produce the hormone glucagon. Glucagon has the reverse effect of insulin, increasing blood-glucose levels. So, with beta-cells dying and alpha cells proliferating, the rise of blood-glucose levels is rapid and hyperglycaemia is likely.
In obese mice, miRNA-375 was found to be in greater proportion than in normal mice. When the miRNA-375 encoding gene was removed, the obese mice quickly developed diabetes. The missing miRNA-375, being responsible for the expression of growth-responsible genes, was unable to promote beta-cell proliferation. The obese mice are particularly dependent upon large beta-cell mass to produce more insulin as muscle, fat and liver cells resist the hormone's effects (insulin resistance being a characteristic of type II diabetes). Thus, the progressive decrease of the beta-cell mass and consequent lowering of insulin secretion led to high levels of blood-glucose resulting in diabetes.
With the mechanisms of miRNA-375 to be further investigated, it is probable that this new understanding of genetics will lead to more effective treatments of diabetes. Another aspect of this topic is antagomirs which act to "silence" or inactivate gene-expressing microRNA's. With the possibility of making use of microRNA's via antagomirs or other biomedical means, there is much potential for this only young knowledge to assist in combating many diseases, not only diabetes.
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"Diabetes: MicroRNA Protects Beta-Cells" ScienceDaily April 25 2009 <http://www.sciencedaily.com/releases/2009/04/090425203534.htm>.
