New discoveries reveal how insulin moves around the body

by Barbara Hewitt on February 6, 2018

Scientists in the United States are working towards potential more effective targeted new treatments for insulin resistance, the condition that usually precedes the development of type 2 diabetes.

Research from the University of Vanderbilt in Nashville has provided new insights into how insulin exits the bloodstream to metabolise glucose in cells.

How Does Insulin Work


They used a new microscopy technique alongside mathematical models to directly measure and characterise the movement of insulin as it traversed blood vessel walls into skeletal muscle cells in live mice.

Their findings suggest that the mechanism of insulin transport as it leaves the tiny blood vessels, or capillaries, in muscle tissue is different to that suggested by previous studies.

‘Defining how insulin leaves the capillary is essential to understanding and treating insulin resistance,’ said senior study author David Wasserman, a professor in molecular physiology and biophysics at the university.

Insulin resistance develops when the cells that make up the tissues of the liver, fat, and muscles do not respond effectively to insulin, the hormone that helps them to convert glucose into energy. The pancreas compensates by making more insulin to keep glucose at the correct level.

But as time goes on, pancreatic cells cannot keep up, glucose levels rise, and prediabetes and type 2 diabetes develop and while it is not clear exactly what causes insulin resistance, research suggest that being physically inactive and overweight are major contributors.

This new research found that the ability of insulin to stimulate glucose uptake in muscle cells depends on the rate at which insulin gets through the endothelium, a thin layer of tissue that lines the blood vessels and controls movement of substances in and out of the bloodstream.

The researchers also found evidence that impairment in the delivery of insulin to muscle cells is a feature of diet induced insulin resistance.

Some studies have suggested that the mechanism of insulin transport is ‘saturable’, that is, that the rate drops off with increasing levels of insulin and that it depends on the presence of insulin receptors on the cells of the endothelium.

However, this study found ‘convincingly’ that insulin movement across the endothelium is non-saturable and does not require the insulin receptor. It concludes that the mechanism works by what they call ‘fluid phase transport’ which may be a convective movement of insulin through the junctions between cells in the endothelium, or a nonspecific vesicular process, or a combination of both.

Wasserman and fellow researchers hope that by improving the understanding at the cellular and molecular level of how insulin exits the capillaries could lead to new ways to reverse insulin resistance, including drugs based on small molecules that boost insulin delivery and new synthetic versions of insulin that reach muscle cells more effectively.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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