A novel insulin that automatically adjusts blood sugar may mitigate some of the complications associated with insulin dosing for patients with type 1 diabetes…
Self-administered insulin is the most important therapeutic to provide control over blood glucose levels for patients with type 1 diabetes. However, standard insulin therapy introduces a number of complications and subsequent issues with control of blood glucose levels. Researchers from MIT, Cambridge, MA, have prepared a derivative of insulin with a molecular switch to provide glucose-mediated activation of the insulin molecule, toward the generation of more autonomous therapy with improved blood glucose control.
The team created Ins-PBA-F, a long-lasting “smart” insulin that self-activates when blood glucose levels rise. Results from diabetic mouse models showed that one injection works for a minimum of 14 hours. Throughout this period, the synthetic insulin appeared to repeatedly and automatically lower blood glucose after mice were given amounts of sugar that were comparable to what would be consumed during a meal.
Ins-PBA-F may be quicker and more effective in lowering blood glucose than long-acting insulin detemir, according to the researchers, who also noted that the speed and kinetics of bringing blood glucose down to safe levels were identical in diabetic mouse models treated with Ins-PBA-F and healthy mice whose blood glucose is regulated by their own insulin.
Co-first author Danny Chou, PhD, of the University of Utah, said in a press release, “This is an important advance in insulin therapy.” “Our insulin derivative appears to control blood sugar better than anything that is available to diabetes patients right now.”
Dr. Chou also said that he will continue evaluating the long-term safety and efficacy of Ins-PBA-F, with the insulin derivative potentially entering phase 1 human clinical trials in 2 to 5 years.
At present, there is no clinically approved glucose-responsive modified insulin. Matthew Webber, PhD, from the Massachusetts Institute of Technology and co-first author with Chou, said in the release. “The development of such an approach could contribute to greater therapeutic autonomy for diabetic patients.”
The researchers created Ins-PBA-F using a long-acting insulin derivative that has a chemical moiety, phenylboronic acid (PBA), added to one end.
“Before, a ‘smart’ insulin really meant delivering insulin differently,” Dr. Chou said. “Ins-PBA-F fits the true definition of ‘smart’ insulin, where the insulin itself is glucose responsive. It is the first in its class.”
Because Ins-PBA-F is a chemically modified version of a naturally occurring hormone, it is likely to be sufficiently safe for daily use, according to Dr. Chou.
- Results from diabetic mouse models showed that one injection works for a minimum of 14 hours.
- Ins-PBA-F, acts more quickly, and is better at lowering blood sugar, than long-acting insulin detemir.
- 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.
Danny Hung-Chieh Chou. Glucose-responsive insulin activity by covalent modification with aliphatic phenylboronic acid conjugates, PNAS, Feb 24, 2015, doi: 10.1073/pnas.1424684112