New injectable product shows promise for preventing and treating hypoglycemia

People with diabetes take insulin to reduce high blood sugar. However, if glucose levels drop too low (due to taking too much insulin or consuming too little sugar), people can experience hypoglycemia, which can lead to dizziness, cognitive impairment, convulsions or coma. To prevent and treat this disease, researchers ACS Central Science report encapsulating the glucagon hormone. In tests on mice, the nanocapsules activated when blood sugar levels fell dangerously and quickly restored glucose levels.

Glucagon is a hormone that signals the liver to release glucose into the bloodstream. It is usually given by injection to combat severe hypoglycemia in people with diabetes. Although an emergency injection of glucagon can correct blood sugar levels in about 30 minutes, the formulations can be unstable and insoluble in water. In some cases, the hormone breaks down quickly when mixed for injections and clumps together to form toxic fibrils. Additionally, many hypoglycemic episodes occur at night, when people with diabetes are not likely to test their blood sugar.

To improve the stability of commercial glucagon and prevent hypoglycemia, researchers Andrea Hevener and Heather Maynard turned to micelles: nanoscale, soap-like bubbles that can be customized to assemble or disassemble in different environments and are used for drug administration.

They developed a glucose-sensitive micelle that encapsulates and protects glucagon in the blood when sugar levels are normal, but dissolves if levels fall dangerously. To prevent hypoglycemia, the micelles could be injected in advance and circulated in the bloodstream until needed.

In laboratory experiments, the researchers observed that the micelles disassembled only in liquid environments mimicking the hypoglycemic conditions of the human body and mice: less than 60 milligrams of glucose per deciliter. Then, when mice suffering from insulin-induced hypoglycemia were injected with specialized micelles, they reached normal blood sugar levels within 40 minutes.

The team also determined that the glucagon-filled micelles remained intact in the mice and did not release the hormone unless blood sugar levels fell below the clinical threshold for severe hypoglycemia. From additional toxicity and biosafety studies in mice, the researchers note that the empty micelles did not trigger an immune response or cause organ damage.

Although more studies are needed, the researchers say their proof of concept is a first step toward a new, effective, on-demand method for preventing or alleviating critically low blood sugar levels.