Team:BGU Israel/Project/Intelligent Medication

Treating the Insulin resistance in liver: background the connection between PTP1B and metabolic syndrome : According to recent studies, a process that takes place in the body with weight gain is an increase in resistance to insulin. The main role of insulin is to remove the glucose from the blood and transfer it into body cells. Resistance of body cells to insulin which leads to a raise in blood sugar and insulin levels. Hyperglycemia increases the risk of diabetes type 2, heart disease and blood vessels. Increase in the level of insulin in the blood leads to an increase in the fatty tissues of the body Insulin resistance shows significant decrease in the downstream reaction of insulin signal transduction, occurs due to attenuated or diminished signaling from the receptors. Based on many studies in the field of mouse and human genetic and chemical inhibitor, it has been found that protein tyrosine phosphatase 1B (PTP1B) has a major influence on insulin signaling by dephosphorlation of the insulin receptor, tyrosyn Kinase, and therefor inactivating it. In addition, insulin receptors activity can be enhanced by the inhibition of PTP1B.

What problem do we solve and why wasn’t it done before? With today’s advanced tools and knowledge scientist are able to inhibit or silence specific genes in a systemic way, which can cause one many side effects, and in some tissues it can cause damage. The main reason that PTP1B is not silenced in all body tissues is we don’t always know what the effect will be in different cell types.

Silencing this protein expression specifically in liver tissue enables us to minimize the unknown effects PTP1B might have in different tissues, effects we might be unaware off and might harm body functions, and on the other hand can help us inhibit it’s function only in liver cells. The connection between PTP1B , diabetes and obesity has led us to try inhibit this protein’s effect by interference RNA mechanism, but only in liver cells, where it causes damage.

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recently it is more common to use the interference RNA mechanism in order to silence gene expression in a systemic manner. but what can we do if the gene we are looking to silence is only harmful in a specific tissue? this is why we focused on the liver function and gene expression and found that apolipoprotein 3 is highly expressed in the liver cells compared to other tissues. we will silence PTP1B using RNA interference and unique hairpin structure that will open as response to apolipoprotein 3 trigger, this molecule present naturally in the liver cells . For this trial, we programmed a software that can plan the best- preferred sequence for building the hairpin, given the target and the trigger gene and using on-line relevant information. This new tool can be a great facilitation for different and variant research purposes.

Click on the picture to check out the machanism

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