Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel "Smart" Insulin Automatically Adjusts Blood Sugar in Diabetic Mouse Model

10.02.2015

Long-acting, glucose-responsive insulin derivative outperforms existing injectable insulin

For patients with type 1 diabetes (T1D), the burden of constantly monitoring their blood sugar and judging when and how much insulin to self-inject, is bad enough. Even worse, a miscalculation or lapse in regimen can cause blood sugar levels to rise too high (hyperglycemia), potentially leading to heart disease, blindness and other long-term complications, or to plummet too low (hypoglycemia), which in the worst cases can result in coma or even death.


Matthew Webber

Scientists have developed a smart insulin that self-activates in response to blood sugar levels. When blood sugar is high, the insulin becomes active, working quickly to normalize blood sugar levels. One injection of the smart insulin, called Ins-PBA-F, can repeatedly and automatically normalize blood sugar levels over a minimum of 14 hours in mice with a type 1 diabetes-like condition. Scientists are now developing the modified insulin into a therapy suitable for human use. Doing so would greatly improve the health and quality of life for diabetics.

To mitigate the dangers inherent to insulin dosing, a University of Utah biochemist and fellow scientists have created Ins-PBA-F, a long-lasting “smart” insulin that self-activates when blood sugar soars. Tests on mouse models for type 1 diabetes show that one injection works for a minimum of 14 hours, during which time it can repeatedly and automatically lower blood sugar levels after mice are given amounts of sugar comparable to what they would consume at mealtime.

Ins-PBA-F, acts more quickly, and is better at lowering blood sugar, than long-acting insulin detimir, marketed as LEVIMIR. In fact, the speed and kinetics of touching down to safe blood glucose levels are identical in diabetic mouse models treated with Ins-PBA-F and in healthy mice whose blood sugar is regulated by their own insulin. A study showing these findings will be published Feb. 9 in PNAS Early Edition.

"This is an important advance in insulin therapy," says co-first author Danny Chou, Ph.D., USTAR investigator and assistant professor of biochemistry at the University of Utah. “Our insulin derivative appears to control blood sugar better than anything that is available to diabetes patients right now.” He will continue evaluating the long-term safety and efficacy of Ins-PBA-F. The insulin derivative could reach Phase 1 human clinical trials in two to five years.

“At present, there is no clinically approved glucose-responsive modified insulin,” says Matthew Weber, Ph.D., co-first author with Chou and Benjamin Tang, Ph.D., who performed the work together while postdoctoral fellows at MIT in collaboration with senior authors and MIT professors Robert Langer, Ph.D., and Daniel Anderson, Ph.D. “The development of such an approach could contribute to greater therapeutic autonomy for diabetic patients.”

The hallmark symptom of diabetes is inadequate control of blood sugar. The deficit is most pronounced in type 1 diabetes, which develops when insulin-producing beta-cells of the pancreas are destroyed. Without insulin, there is no way to shuttle sugar out of the blood and into cells, where it is used for energy. T1D patients depend on daily insulin injections for survival.

Despite advances in diabetes treatment such as insulin pumps and the development of four types of insulin, patients must still manually adjust how much insulin they take on a given day. Blood sugar levels vacillate widely depending on a number of factors such as what someone chooses to eat and whether they exercise.

A glucose-responsive insulin that is automatically activated when blood sugar levels are high would eliminate the need for additional boosts of insulin, and reduce the dangers that come with inaccurate dosing. Various such “smart” insulins under development typically incorporate a protein-based barrier, such as a gel or coating, that inhibits insulin when blood sugar is low. However, such biologically based components are often sources of trouble, provoking unwanted side effects such as an immune response.

Ins-PBA-F differs in that it was created by chemically modifying insulin directly. Ins-PBA-F consists of a long-acting insulin derivative that has a chemical moiety, phenylboronic acid (PBA), added to one end. Under normal conditions, Ins-PBA-F binds to serum proteins that circulate in the bloodstream, blocking its activity. When blood sugar levels are high, glucose sugars bind PBA, which acts like a trigger to release Ins-PBA-F so it can get to work.

“Before, a ‘smart’ insulin really meant delivering insulin differently,” says Chou. “Ins-PBA-F fits the true definition of ‘smart’ insulin, where the insulin itself is glucose responsive. It is the first in its class.”

Chou explains that because Ins-PBA-F is a chemically modified version of a naturally occurring hormone, he thinks it is likely to be safe enough to use on a daily basis, similar to other insulin derivatives that are on the market today.

“My goal is to make life easier, and safer for diabetics,” he says.

This work was supported by the Leona M. and Harry B. Helmsley Charitable Trust, the Tayebati Family Foundation, the National Institutes of Health, and the Juvenile Diabetes Research Foundation.

Glucose-responsive insulin activity by covalent modification with aliphatic phenylboronic acid conjugates. Danny Hung-Chieh Chou, Matthew J. Webber, Benjamin C. Tang, Amy B. Lin, Lavanya S. Thapa, David Deng, Jonathan V. Truong, Abel B. Cortinas, Robert Langer, and Daniel Anderson. PNAS Early Edition, Feb. 9, 2015

Contact Information
Julie Kiefer
Communications Specialist
jkiefer@neuro.utah.edu
Phone: 801-597-4258

Julie Kiefer | newswise
Further information:
http://unews.utah.edu/

Further reports about: Health Sciences Insulin blood sugar mouse models sugar type 1 diabetes

More articles from Health and Medicine:

nachricht Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

nachricht Prospect for more effective treatment of nerve pain
20.02.2017 | Universität Zürich

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>