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Smart insulin and new hope for type-1 diabetes

• A new smart insulin could improve the lives of people with type-1 diabetes 

• The smart insulin is easier, faster, and more effective than current therapies

• The new compound automatically activates in response to rising blood sugar

A new compound, Ins-PBA-F, referred to as ‘smart insulin’, could spare people living with type-1 diabetes the burden of frequently injecting, and constantly monitoring their blood sugar levels.

The new compound, developed by scientists from the University of Utah, USA, and reported in a 2015 edition of the Proceedings of the National Academy of Science, automatically activates when your blood sugar level soars, brings it back to normal, and remains in circulation for up to 24 hours. In the future, people with type-1 diabetes could inject the smart insulin once a day, or even less frequently, overcoming the need for constant self-monitoring, and insulin top-ups after meals.
 

Easier, faster and more effective

Researchers suggest that the speed, and chemical reactions of Ins-PBA-F normalizing blood sugar in diabetic mice is the same as in healthy mice responding to blood sugar changes with their own insulin. Ins-PBA-F could give a faster, more effective response to lowering blood sugar than the current long-acting insulin drug, and could be tested in humans in two to five years.
 

Type-1 diabetes

According to the WHO, in 2014, 9% of all adults have diabetes, and an estimated 10% of these have type-1 diabetes, a significant proportion of which are children. Type-1 diabetes is an autoimmune disease in which the body kills off all its pancreatic beta cells, which produce insulin that regulates blood sugar. Without beta cells, the body’s sugar levels fluctuate wildly. Dr Sufyan Hussain, Senior Lecturer in Diabetes, Endocrinology and Metabolism at Imperial College, London, describes type-1 diabetes:

       
 

Unrelenting regimen

While insulin injections or infusion allow a person with type-1 diabetes to stay alive, and lead a full and active life, they neither cure the disease, nor necessarily prevent the possibility of the disease’s serious effects, which may include: kidney failure, blindness, nerve damage, heart attack, stroke and pregnancy complications. Traditional insulin therapies are a constant management challenge. Patients must carefully balance insulin doses with eating and other activities multiple times a day and night. Hussain describes the genesis, and benefits of insulin therapy:

    
 

Advantages of ‘smart insulin’

Without insulin, the body has no mechanism for moving sugar out of the blood and into cells, where it is used for energy. People with type-1 diabetes are completely dependent on their daily insulin injections for their survival, and have to check their blood-glucose level by pricking their fingers several times a day to assess how much insulin to inject. Any lapse or miscalculation in this unrelenting regimen can run the risk of dangerous high and low blood-glucose levels; both of which can be life threatening.

“In theory, with Ins-PBA-F there would be none of these glucose problems,” said co-author Dr Danny Chou, “A smart insulin drug that automatically activates in response to rising blood sugar would get rid of the need for top-up injections of insulin, and eliminate the danger of incorrect dosing”.
 

Takeaways

Ins-PBA-F closely mimics the way bodies return their blood sugar levels to normal after eating. According to Chou, “This is an important advance in insulin therapy. Diabetic patients still need to guess to some extent how much insulin they need. With Ins-PBA-F you would just inject it, and it wouldn’t matter if you overshot because its activity would stop when glucose levels get too low. Our smart insulin derivative appears to control blood sugar better than anything that is available to diabetes patients right now.”

• Promising animal study suggests a vaccine for type-1 diabetes
• Harvard’s Dana Faber Cancer Institute endorses the study
• Lab spent years detailing the molecular immune system's response to insulin
• The therapy for type-1 diabetes is insulin, but there’s no cure
• Living with type-1 diabetes is a constant challenge

A molecule that prevents type-1 diabetes in mice has provoked an immune response in human cells, according to scientists from the National Jewish Health and the University of Colorado. The findings, published in the 2015 Proceedings of the National Academy of Sciences, suggest that a mutated insulin fragment could be used to prevent type-1 diabetes in humans.
 

Strategies that work in mice often fail in humans 

Previously, researchers tried administering insulin to people at risk of the disease as a form of immunotherapy similar to allergy injections, but this didn’t provoke an effective response. John Kappler, Professor of Biomedical Research at National Jewish Health says, "Our findings provide an important proof of concept in humans for a promising vaccination strategy." In 2011, researchers from Harvard University’s Dana Farber Cancer Institute reported that Kappler’s strategy prevented type-1 diabetes in mice. However, strategies that work in mice often fail in humans.
 

Promising findings

Kappler’s findings suggest that an insulin fragment with a change to a single amino acid could provoke an immune response. The idea comes from work in Kappler's laboratory detailing the molecular immune system's response to insulin. This suggests that mutating one amino acid in an insulin fragment, and then presenting the insulin to the immune system, might provoke better recognition by the immune system.

Researchers mixed a naturally occurring insulin fragment, and the mutated insulin fragment with separate cultures of human cells. They found that human T-cells responded minimally to the naturally occurring insulin fragment, but relatively strongly to the mutated one. The human T-cells produce both pro-inflammatory and anti-inflammatory chemicals known as cytokines, and scientists believe that healthy immune responses balance pro- and anti-inflammatory factors. Autoimmune disease occurs when the pro-inflammatory response dominates.
                           

Type-1 diabetes

Type-1 diabetes is an autoimmune disease in which a person’s pancreas stops producing insulin, a hormone that enables individuals to get energy from food. It occurs when the body’s immune system attacks and destroys the insulin producing cells in the pancreas, called beta cells. The causes of type-1 diabetes are not fully understood, but scientists believe that both genetic and environmental factors are involved. Dr Sufyan Hussain of Imperial College, London explains:


     

      (click on the image to play the video) 

Type-1 diabetes most typically presents in early age with a peak around the time of puberty. Historically the condition has been most prevalent in populations of European origin, but is becoming more frequent in other ethnic groups. Kuwait, for example, now has an incidence of 22.3/100,000. India and China have relatively low incidence rates, but account for a high proportion of the world’s children with type-1 diabetes because of their large populations. 
 

Living with type1 diabetes

Living with type-1 diabetes is a constant challenge. People with the condition must carefully balance insulin doses (either by multiple injections every day or continuous infusion through a pump) with eating and other activities throughout the day. They must also measure their blood-glucose levels by pricking their fingers for blood six or more times a day. Despite this constant attention, people with type-1 diabetes run the risk of high or low blood-glucose levels, both of which can be life threatening. People with type-1 diabetes overcome these challenges on a daily basis. While insulin injections or infusions allow a person with the condition to stay alive, they don’t cure the disease, nor do they necessarily prevent the possibility of the disease’s complications, which may include kidney failure, blindness, nerve damage, heart attack, stroke, and pregnancy complications. Richard Lane, President of Diabetes UK, and a person living with type-1 diabetes, describes some of the lifestyle changes associated with the condition:

       

        (click on the image to play the video)
 

Takeaways

While Kappler’s results don’t prove that the mutated insulin fragment will work as a vaccine in humans, they do demonstrate a response in humans consistent with the vaccination response in mice. "The new findings confirm that the painstaking work we have done to understand the unconventional interaction of insulin and the immune system has relevance in humans and could lead to a vaccine and a treatment for diabetes," says Kappler.