Diabetes: microRNAs regulate insulin sensitivity
Zurich – Overexpression of two microRNAs trigger development of insulin resistance, a hallmark of type II diabetes which affects about 20% of the elderly (aged 55-74) in the western world. In Nature, a research team headed by Markus Stoffel from ETH Zurich and Regulus, a joint venture of Alymnan and Isis Therapeutics, reported yesterday that overexpression of the intronic microRNAs miR103 and mi107 made the insulin receptors on fat and liver cells of obese mice insensitive to the peptide hormone signal and raised blood glucose levels. The effect seems to be mediated by Caveolin-1, which regulates insulin signalling through receptor stabilisation. Targeting of antisense drugs – so called antagomirs – specifically against miR103 and mi107 reversed the effect and restored glucose sensitivity and increased glucose uptake both in mice as well as in human cell cultures. The effect was more pronounced in adipose cells than in liver cells because they contain more Caveolin-1. According to Stoffel, a scientific advisor of Regulus, however it is a long way from the current preclinical stage to establishment of an effective treatment. Insulin resistance develops before type 2 diabetes is established. Insensitivity against insulin on fat and muscle cells blocks glucose uptake into the cells and triggers dissimilation of intracellular triglycerides. At the same time it disturbs regulation of blood glucose levels by liver cells that normally regulate glucose homeostasis by the rate of glucose storage and glycogen dissimilation.