Novel ‘Smart’ insuling for patients with type 1 diabetes eliminates the burden of constantly monitoring their blood sugar, self-injecting and even worse, a miscalculation.
Lapse in regimen leads to high blood sugar levels (hyperglycemia), potentially leading to heart disease, blindness and other complications, or it leads to too low levels (hypoglycemia), which can result in coma or even death.
To overcome the dangers of insulin dose intake, a University of Utah biochemist and his team have created Ins-PBA-F, a “smart” insulin that self-activates when blood sugar goes up.
Their trials 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, which is 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.
“This is an important advance in insulin therapy,” says Danny Chou, USTAR investigator and assistant professor of biochemistry at the University of Utah. 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 Webber, co-first author with Chou and Benjamin Tang, who performed the work together while post-doctoral fellows at MIT in collaboration with senior authors and MIT professors Robert Langer and Daniel Anderson.
The main problem with diabetes is inadequate control of blood sugar level. The deficit is most pronounced in type 1 diabetes, in which insulin-producing beta-cells of the pancreas are destroyed. T1D patients virtually depend on daily insulin injections for their survival.
Despite advances and insulin pumps or inhalers, patients must still manually adjust how much insulin they take on a given day and blood sugar levels vacillate widely depending on what one eats or whether they exercise or not.
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, said researchers.
So far, many such “smart” insulins developed focused typically on a protein-based barrier, such as a gel or coating, that inhibits insulin when blood sugar is low but they lead t side effects such as immune response, said the Utah team.
Ins-PBA-F differs in that it was created by chemically modifying insulin directly and it 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 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.”
Since Ins-PBA-F is a chemically modified version of a naturally occurring hormone, Chou says that it is likely to be safe enough to use on a daily basis, similar to other insulin derivatives that are in the market today.
The study was published in PNAS Early Edition.