A new nanomedicine may prevent severe hypos in diabetics

Nanosized particles that release glucagon, the hormone responsible for raising blood glucose levels, on-demand could mean that diabetics don’t need to worry about potentially dangerous low blood sugar levels, according to new research.

For diabetics, hypoglycemia – low blood glucose – is common, especially for those taking insulin. It’s also life-threatening. Severe hypoglycemia can cause a person to feel confused, pass out, or have a seizure. Not all diabetics are ‘hypo aware,’ which increases the risk of serious complications.

Beta cells in the pancreas produce the hormones insulin and glucagon; the former decreases blood glucose, and the latter increases it. A commercialized injectable version of glucagon exists as an emergency treatment for hypoglycemia and is usually used when a diabetic person is unconscious. But what if severe hypoglycemia could be avoided altogether? Researchers from UCLA have developed a nanomedicine that may just achieve that.

Normal fasting blood glucose levels are between 70 mg/dL (3.9 mmol/L) and 100 mg/dL (5.6 mmol/L). Hypoglycemia is defined as a blood glucose below 70 mg/dL. The pancreas releases glucagon when blood glucose drops, which instructs the liver to release stored glucose to raise blood glucose.

While there are several materials that sense and respond to high glucose levels by releasing insulin, systems that deliver glucagon when they detect low glucose levels are less common. In the present study, the researchers used glucagon encapsulated by micelles – nanoscale spheres made of substances that are soluble in water and can carry other substances inside them – that had been developed to respond to blood glucose.

Testing their glucagon-packed micelles in lab experiments, the researchers found that they disassembled and released glucagon only in liquid environments that mimicked hypoglycemia in humans and mice – a blood glucose of less than 60 mg/dL (3.3 mmol/L). Mice with insulin-induced hypoglycemia treated with an injection of the micelles achieved normal blood sugar within 40 minutes.

Additionally, they observed that if the micelles containing glucagon were injected into mice not in response to a hypoglycemic event, they remained intact and didn’t release the hormone unless blood glucose levels fell below the clinical threshold for severe hypoglycemia. Once they’d been emptied of glucagon, the micelles did not trigger an immune response or cause organ damage.