Micro RNA and Diabetes

Micro RNA is becoming an interesting element of gene expression. In a recent Science article they show how one of the micro RNAs controls HDL in the metabolic syndrome an off shoot of Type 2 Diabetes.

The article states:

In humans, insulin resistance is a hallmark of metabolic syndrome, which is provoked by obesity. In addition to hyperinsulinemia, hyperglycemia, and fatty liver, cardinal features of metabolic syndrome include an increase in plasma triglyceride levels, owing to elevated very-low-density lipoproteins (VLDL), and a decrease in plasma HDL.

Low HDL is believed to contribute to the increase in coronary heart disease in these subjects. Evidence suggests that the hypertriglyceridemia is caused by the insulin-induced increase in SREBP-1c mRNA and protein.

Is it possible that the reduction in HDL is caused by a decrease in ABCA1, owing to the increased production of miR-33b from the insulin-stimulated SREBP-1c gene? Unfortunately, this question cannot be answered by study of hepatic miR-33b in the usual models of insulin resistance in obese rats or mice, because the SREBP-1c genes of these model animals lack miR-33b.

This is consistent with the observation that obese insulin-resistant mice manifest all of the cardinal features of metabolic syndrome except a reduction in HDL. Here is a situation where geneticists may come to the rescue, by searching for mutations in miR-33b in patients with metabolic syndrome who manifest inappropriately elevated HDL. Alternatively, the hypothesis can be tested by treating metabolic syndrome subjects with agents that antagonize miR-33b and testing for increased HDL.

One suspects that the simple Watson and Crick model may have to be dramatically changed to handle all of these micro RNA changes. The micro RNAs may very well become the research focus of the next decade.