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A new technique that uses modified insulin and red blood cells to create a glucose-responsive insulin (GRI) delivery system has been developed by researchers from North Carolina State University and the University of North Carolina in the USA. The new technique effectively reduced blood sugar levels for more than 48 hours in mice that had type 1 diabetes.

A/Prof Zhen GuThe researchers, led by Prof Zheng Gu, modified insulin by chemically binding it to a glucose derivative called glucosamine. The glucosamine could then bind to glucose transporters on the surface of a red blood cell, effectively attaching the insulin to the blood cell. The end result is a red blood cell studded with insulin molecules.

Once in the bloodstream, the blood cells carrying insulin interact with their environment. If glucose levels are high, glucose molecules effectively displace the glucosamine in the blood cells’ glucose transporters. And when the glucosamine is set free from the blood cell, so is the insulin.

The insulin can then trigger the process that reduces glucose levels in the blood.

In the study, researchers compared mice receiving the modified insulin and blood cell system to three other groups: a group that received placebo saline solution; a group that got only modified insulin; and a group that got a mixture of unmodified insulin and red blood cells.

The researchers found that the type 1 diabetic mice that received the modified insulin and blood cell system had significantly reduced blood glucose levels for more than two days.

modified insulin and red blood cells interact

The researchers also tested each of the drug combinations in a group of healthy mice, and found that the modified insulin and blood cell system reduced the risk of hypoglycaemia compared to the other drug combinations.

In addition, the researchers conducted an experiment in the type 1 diabetic mice using modified insulin and tiny particles called nanoparticles that had been coated with red blood cell membranes. The modified insulin and nanoparticle system achieved comparable results to those found using modified insulin and red blood cells.

Next, they will further test these concepts in mice to gather enough data to determine if this idea can be taken into human clinical trials.  The team is also exploring the use of painless microneedles to deliver this system.

JDRF’s GRI research journey

JDRF has proudly supported GRI research since the initial concept emerged in the early 2000s.

In 2003, a Massachusetts Institute of Technology chemical engineer founded a company called SmartCells to develop a glucose-responsive insulin. Others were skeptical, but JDRF saw tremendous promise and provided funding to encourage its development. In 2010, our judgment was validated when SmartCells was acquired by Merck, which is now testing the resulting glucose-responsive insulin in an early stage clinical trial in the US.

JDRF is continuing to fund research of glucose-responsive insulin and we are making headway with several projects. In 2016, JDRF partnered with Sanofi to commit almost $5 million to GRI research. You can read more about this partnership here.

What’s happening in Australia?

JDRF-awarded researchers at Monash University in Victoria, led by Dr Christoph Hagemeyer, are  investigating smart insulin delivery with targeted glucose responsive nanomaterials.

The system will use cutting-edge chemical engineering technology to design nanoparticles to store insulin, and to degrade and leave no residue once insulin has been released. These nanoparticles will also be designed so that they ‘home’ to the circulation of the liver in order to achieve insulin delivery similar to that seen in people without type 1 diabetes, and will be tested in animal models during this phase of research. Finding the most effective delivery system and the best dose will help design future clinical trials in humans. The ultimate goal is glucose-responsive insulin which would only be activated when glucose levels are high.

JDRF continues to support GRI trials globally and is watching this space closely for any advancement.

 

Photo credit: University of North Carolina at Chapel Hill School of Medicine

 

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