People with diabetes use insulin to manage high blood sugar levels. However, if their glucose levels drop too much—due to excessive insulin intake or insufficient sugar consumption—they may face hypoglycemia. Symptoms of this condition can include dizziness, confusion, seizures, or even loss of consciousness. To combat and manage this issue, researchers have developed a method to encapsulate the hormone glucagon. In experiments with mice, these nanocapsules activated when blood sugar levels fell to critical lows and rapidly elevated glucose levels.
People with diabetes use insulin to manage high blood sugar levels. However, if their glucose levels drop too much—due to excessive insulin intake or insufficient sugar consumption—they may face hypoglycemia. Symptoms of this condition can include dizziness, confusion, seizures, or even loss of consciousness. To combat and manage this issue, researchers in ACS Central Science have developed a method to encapsulate the hormone glucagon. In experiments with mice, these nanocapsules activated when blood sugar levels fell to critical lows and rapidly elevated glucose levels.
Glucagon is a hormone that instructs the liver to release glucose into the bloodstream. It is usually administered through injection to treat severe hypoglycemia in diabetic individuals. Although an emergency glucagon shot can stabilize blood sugar levels in about half an hour, existing formulations may be unstable and may not dissolve well in water. In some instances, the hormone can break down quickly when prepared for injections and may form harmful clumps known as fibrils. Additionally, many instances of hypoglycemia occur at night when diabetic individuals may not check their blood sugar levels. To enhance the stability of commercial glucagon and avert hypoglycemia, researchers Andrea Hevener and Heather Maynard turned to micelles—tiny, soap-like bubbles that can be tailored to either assemble or disassemble in various settings and are typically used for drug delivery. They created a glucose-responsive micelle that safeguards glucagon in the bloodstream when sugar levels are normal but disintegrates if levels fall dangerously low. To help prevent hypoglycemia, these micelles could be injected in advance and allowed to circulate in the bloodstream until necessary.
In laboratory tests, the researchers found that the micelles only disassembled in liquid conditions that simulated hypoglycemic states in both humans and mice—specifically, with glucose levels below 60 milligrams per deciliter. Following this, mice that were induced with insulin-related hypoglycemia and then injected with the specialized micelles restored normal blood sugar levels within 40 minutes. The team also confirmed that the glucagon-packed micelles remained intact within the mice and did not release the hormone until blood glucose dropped beneath the critical threshold for severe hypoglycemia. Additional studies on toxicity and safety indicated that the empty micelles did not provoke an immune response or cause damage to organs.
Although further research is necessary, the researchers believe that this preliminary work marks a promising beginning for a new, on-demand approach to preventing or alleviating extremely low blood sugar levels.
The authors wish to acknowledge funding from the Leona M. and Harry B. Helmsley Charitable Trust; BioPACIFIC Materials Innovation Platform supported by the National Science Foundation; the National Science Foundation Graduate Research Fellowship Program; the National Institutes of Health; and the Clinical and Translational Science Institute at the University of California, Los Angeles.
