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“Smart” Insulin Used to Prevent Hypoglycemia

Nov 2, 2019

Author: Steve Freed, R.PH., CDE

A new form of insulin, “i-insulin,” working in response to glucose levels.

When medical professionals think of insulin the first adverse effect that comes to their minds is hypoglycemia. Their possible thoughts may be, what if there was an agent or drug that could possibly prevent against these hypoglycemia episodes? Well, bioengineers at the University of California Los Angeles may have found an agent to prevent the risk of hypoglycemia episodes that occur with the use of insulin. The new “i-insulin” is a form of “smart” insulin that has been developed to prevent serious events of hypoglycemia. This “smart” insulin works in response to changing blood glucose levels. Perhaps “i-insulin” may be the future of adjunctive therapy with injectable insulin.

Insulin is a protein hormone produced and released from the beta cells of pancreatic islets when blood glucose begins to rise from the foods consumed. Insulin aids in regulating the body’s blood glucose levels, by uptaking the glucose from the blood into the cells for energy. Patients with diabetes either have a deficiency in insulin secretion, where the body is not producing insulin to be released; or insulin action, where insulin is not effectively being used. This disease affects about 415 million people worldwide. For those with type 1 diabetes or progressive type 2 diabetes, exogenous insulin is injected into the body daily or over continuous infusion to correct this metabolic disorder. 

Normally, blood glucose monitors are used to check a patient’s blood glucose level or help calculate correct insulin dosages. An adequate carbohydrate intake is essential for controlling blood glucose levels. Thus, insulin is used to maintain blood glucose levels, or correct levels become uncontrollable. But the misuse of insulin can pose a severe threat to the body. 

Too much or an overdose of insulin can lead to extremely low blood glucose levels or hypoglycemia. These hypoglycemia episodes can cause serious life-threatening events, such as seizures, coma, or death. That’s when the new development of “i-insulin” can come into play to help prevent the hypoglycemic episodes. 

Makers of this form of “smart” insulin added an additional molecule to the form of insulin, called a glucose transporter inhibitor. This glucose transporter inhibitor blocks the glucose transporter molecule on the cell surface, bringing in the surrounding glucose from the blood into the cell. The inhibitor molecule prevents too much glucose from going into the cell when blood glucose levels are normal. 

Lead researcher, Zhen Gu, a professor of bioengineering at University of California Los Angeles (UCLA) Samueli School of Engineering, described the i-insulin as working like a “smart key.” An insulin conjugate consisting of an insulin analog was attached to an insulin facilitated glucose transporter inhibitor developed by the UCLA researchers. The glucose transporter inhibitor can reversibly bind to the glucose transporter receptor on the cell’s surface. The molecule is glucose- responsive, meaning how strongly it binds to the glucose receptor varies depending on the concentration of the blood glucose.

UCLA researchers explained the mechanism of the smart insulin binding force on the glucose transporter receptor as being dependent upon the glucose concentrations. The insulin analog -glucose transporter complex separates when blood glucose levels rise after a meal. After detachment the free insulin analog thereafter binds to the insulin receptor to activate the glucose transporter to move glucose from the bloodstream into the cell. In any event of overdosing with an injectable insulin, the formation of the reversible glucose-responsive insulin analog and glucose transporters complexes temporarily blocks the glucose transporter molecules, subsequently decreasing the chance of experiencing a hypoglycemic episode.

“i-insulin” was first assessed in a vitro system using erythrocyte ghosts. The form of insulin was then studied in drug-induced mice with type 1 diabetes throughout a series of tests. The mice were given native insulin which maintained euglycemic for 4 hours, meanwhile animals were given a single subcutaneous injection of i-insulin and subjects remained euglycemic for 10 hours. The researchers performed a crossover between the humans and mice for the second treatment three hours after the first treatment. The mice were able to maintain normal blood glucose levels being treated with i-insulin, however the human glucose levels showed hypoglycemia after being treated with native insulin.

Furthermore, the i-insulin still has pharmacokinetics components to be figured out. Onset of action and duration of action are two areas researchers are examining.  The researchers at UCLA suggest that i-insulin be formulated as transdermal microneedle patches or oral pills, which poses uncertainty due to insulin not being ingested orally. The next step in the process of this new development of “insulin” would be to further studies into clinical trials. This latest development could be a game changer in the advancement of diabetes care.

Practice Pearls:

  • Researchers from UCLA have developed a glucose transporter inhibitor form of insulin that temporarily blocks the glucose transporter molecules from moving glucose from the bloodstream into the cell when glucose levels are normal to prevent hypoglycemia.
  • The glucose transporter inhibitor can reversibly bind to the glucose transporter receptor on the cell’s surface.
  • Further studies are progressing to evolve the new form of insulin into clinical trials.

Smart Insulin Could Prevent Hypoglycemia during Diabetes Treatment.” MDLinx, www.mdlinx.com/pharmacy/top-medical news/article/2019/05/17/7567215/ZZ4F022BE73AF540C59958208C58CDBD66?news_id=673&newsdt=052019&subspec_id=282&utm_source=DailyNL&utm_medium=newsletter&utm_content=General-Article&utm_campaign=article-section.

“Smart Insulin for Diabetes Therapy Could Protect against Hypoglycemia.” GEN, 20 May 2019, www.genengnews.com/news/smart-insulin-for-diabetes-therapy-could-protect-against-hypoglycemia/.