Chemistry trick paves way for safer diabetes medication

February 18, 2016, University of Copenhagen
A model of the newly invented self assembling Nano-insulin shows how each insulin hexamer hooks onto the next in a very well organized grid. This should assure, that medication produced with this principle will be released very evenly, thus preventing side-effects. Credit: Knud J. Jensen, University of Copenhagen, Department of Chemistry

New research from the University of Copenhagen points to an entirely new approach for designing insulin-based pharmaceuticals. The approach could open the door for more personalized medications with fewer side effects for Type 1 Diabetes patients.

Knud J. Jensen is a professor at the University of Copenhagen's Department of Chemistry. Together with Technical University of Denmark (DTU) and Novo Nordisk researchers, he has published "Construction of Insulin 18-mer Nanoassemblies Driven by Coordination to Iron (II) and Zink (II) Ions at Distinct Sites" in the renowned journal, Angewandte Chemie.

"We have discovered an entirely new method of modifying a molecule - Insulin - that is important for 35 million . We are incredibly happy with that," says Professor Jensen.

Diabetes occurs when people lose their ability to produce , a protein that regulates blood sugar. Diabetes cannot be cured, and is fatal if untreated. Furthermore, if improperly treated, the illness can lead to serious complications and permanent health consequences. Luckily, injections of manufactured insulin can help patients live nearly normal lives. But there is one catch: producing insulin that can be evenly released throughout the day is problematic. As a result, patients have a tough time maintaining uniform .

Natural insulin assembles into homogenous grid-like structures called hexameres. The great challenge producing insulin medications is to create equally homogenous nanostructures. The more uniformly insulin can be assembled; the more likely it is that it can be released in predictable amounts, and at steady rates.

Researchers at the Department of Chemistry have devised a method that gets manufactured insulin to self-assemble in homogenous chemical grid constructs. Bipyridines sit at the end of all . A bipyridine serves as the hook that insulin uses to hitch onto other molecules. By hooking an Iron II atom to the bipyridine, chemists can control insulin assembly with great precision.

Whereas insulin produced in a body is stored in the pancreas until ready for deployment, diabetes patients inject manufactured insulin under the skin, where it is stored in fatty tissue. Thanks to the newly developed Iron II method, Jensen and his team have persuaded manufactured insulin to self-assemble in nanostructures that are well suited form depots in fat. To study whether their self-assembling nano-insulin could also be released into the bloodstream, Jensen's research team tested the new form of insulin on rats. And their levels fell. This result leaves Professor Jensen optimistic about the new method.

"We have demonstrated that we can influence the manner in which insulin assembles, and we have demonstrated that the insulin can then be released. A great deal of work remains before the principles of our nano-insulin can be translated into a medication. But for me, it is absolutely clear that this could be a good method for designing medications that release over extended periods of time, from depots beneath the skin," says Knud J. Jensen, who continues: "because we are able to control the insulin's self-assembling properties so precisely, I believe that the method can also be used to design insulin with a variety of properties."

Besides studying the effect in rats, the research team also investigated the insulin grid structures using the nanotech methods, Atomic Force Microscopy (AFM) and Small Angle X-ray Scattering. AFM photographs the surfaces of molecules, and Small Angle X-Ray photographs the internal structures. In this way, they have been able to state with certainty that the addition of Iron II really has allowed the insulin to assemble itself into an unusually homogenous manner.

For Professor Jensen though, the chemistry behind the self-assembly is the real kick. "Using Iron II to make proteins self-assemble is a new type of chemical process. That is to say, that we have conducted fundamental research. But we have chosen to conduct our fundamental research on a molecule that is relevant for an important industrial partner. That our fundamental research can lead to the development of new medications makes our work feel all the more relevant," concludes Jensen.

Explore further: Trends in insulin use, glycemic control explored

More information: Henrik K. Munch et al. Construction of Insulin 18-mer Nanoassemblies Driven by Coordination to Iron(II) and Zinc(II) Ions at Distinct Sites, Angewandte Chemie International Edition (2016). DOI: 10.1002/anie.201509088

Related Stories

NAFLD linked to unfavorable metabolic profile in T2DM

February 17, 2016

(HealthDay)—For obese patients with type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD) is associated with an unfavorable metabolic profile, according to a study published online Feb. 9 in Diabetes ...

FDA approves two new medications for diabetes

September 29, 2015

(HealthDay)—Two new diabetes treatments, Tresiba (insulin degludec injection) and Ryzodeg (insulin degludec/insulin aspart injection), have been approved by the U.S. Food and Drug Administration.

Type 2 diabetes drug can exhaust insulin-producing cells

February 11, 2016

Long-term use of liraglutide, a substance that helps to lower blood sugar levels in patients with type 2 diabetes, can have a deteriorating effect on insulin-producing beta cells, leading to an increase in blood sugar levels. ...

Recommended for you

Engineers repurpose wasp venom as an antibiotic drug

December 7, 2018

The venom of insects such as wasps and bees is full of compounds that can kill bacteria. Unfortunately, many of these compounds are also toxic for humans, making it impossible to use them as antibiotic drugs.

Researchers probe hydrogen bonds using new technique

December 7, 2018

Researchers at Carnegie Mellon University have used nuclear resonance vibrational spectroscopy to probe the hydrogen bonds that modulate the chemical reactivity of enzymes, catalysts and biomimetic complexes. The technique ...

Are amorphous solids elastic or plastic?

December 7, 2018

In a crystalline solid, the atoms form an ordered lattice. Crystalline solids respond elastically to small deformations: When the applied strain is removed, the macroscopic stress, as well as the microscopic configuration ...

Molecular insights into spider silk

December 7, 2018

Spider silk is one of the toughest fibres in nature and has astounding properties. Scientists from the University of Würzburg discovered new molecular details of self-assembly of a spider silk fibre protein.

Copycat cells command new powers of communication

December 7, 2018

From kryptonite for Superman to plant toxins for poison ivy, chemical reactions within the body's cells can be transformative. And, when it comes to transmuting cells, UC San Diego researchers are becoming superhero-like ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.