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Breaking the "insulin barrier"

Type 2 diabetes blocks the bloodstream’s ability to distribute insulin to its target cells. That basic malfunction contributing to insulin-resistance makes one in five of us developing the disease at some stage in our lives and cases rising steadily. The IRVASC project, led by Per-Anders Jansson, aims to find out why.

The latest research project, Insulin Resistance Mechanisms in Human Vasculature (IRVASC) aims to answer a big question: what is it about the way the vascular system operates in humans that can cause it to block the very insulin it needs to distribute for the body’s survival? With nine out of ten diabetes patients having type 2, it is overwhelmingly the most prevalent form worldwide. Unlike type 1, where the pancreas fails to make insulin in the first place, type 2 largely involves lack of biologic effects of the insulin that is made – a malfunction known as insulin-resistance.

So we know what happens – but why? To this end, our group is focusing the research on three vascular-related issues: firstly, why does the capillary wall act as a barrier to transfer the insulin into the tissue; secondly, why doesn’t the bloodstream carry insulin to the cells – how do you improve blood flow sufficiently? And thirdly why do muscle cells and fat cells around the body then resist to respond when insulin finally have reached the target cell?

Our group has seen some progress with the compound tadalafil.We’re especially looking at the role of microvascular capillary recruitment after a meal. In a healthy body, blood flow increases after a meal, to distribute insulin to cells. But with type 2, blood flow is impaired and insulin is not distributed to cells in the periphery. Methodology for these studies involves taking adipose tissue samples from patients and healthy control groups and isolating microvascular cells in each. The aim is to discover the mechanism the vascular cells use to transport insulin through the capillary wall, and thus what is failing in the mechanism in diabetes patients.

Our group has seen some progress with the compound tadalafil. This was originally a drug used to combat impotence because it increases blood flow. But we’re seeing encouraging metabolic results when using it to increase blood flow in other areas too. We still need more data on this so it’s an area we will keep pursuing. Though our team is some way off understanding the complete mechanics of the insulin barrier, there has been significant progress towards this goal too. We have then been able to show that insulin-resistance is associated with an impaired signalling system in the key protein downstream the insulin receptor within the microvascular endothelium.

Ultimately, we all have one aim – to identify and understand the various factors that cause type 2 diabetes and find a way of preventing a disease that can show itself at any stage in a person’s life. Because at best it is a disease dramatically reducing the quality of life for millions of people around the world. At worst it is threatening the lives of millions more.

Contact Information

Per-Anders Jansson

The Wallenberg Laboratory, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden

Visiting Address:
Bruna Stråket 16

Phone:
46 (0)70 203 30 10

Fax:
46 (0)31-82 37 62

Page Manager: Anna Hallén|Last update: 5/3/2012
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