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Artificial Beta Cells Shown to Produce Insulin as Needed

Zhen Gu

Zhen Gu (University of North Carolina, Chapel Hill)

31 October 2017. A biomedical engineering team developed artificial beta cells that in animal tests perform similar to natural cells in the pancreas to produce insulin as needed for controlling blood glucose levels. Researchers from a joint medical and engineering program at University of North Carolina in Chapel Hill and North Carolina State University in Raleigh describe their discovery in yesterday’s issue of the journal Nature Chemical Biology (paid subscription required).

The team led by biomedical engineering professor Zhen Gu and endocrinologist John Buse are seeking more patient-friendly and economical solutions for people with type 1 and type 2 diabetes who regularly need external sources of insulin for controlling their blood glucose levels, a number estimated at 6 million in the U.S. These individuals today must continuously monitor their blood glucose levels, regularly inject insulin, be outfitted with insulin pumps, or receive transplanted beta cells that produce insulin.

Diabetes is a chronic disorder where the pancreas does not create enough insulin to process the sugar glucose to flow into the blood stream and cells for energy in the body. In type 2 diabetes, which accounts for at least 90 percent of all diabetes cases, the pancreas produces some but not enough insulin, or the body cannot process insulin. Type 1 diabetes is an autoimmune condition, where the immune system attacks healthy beta cells in the pancreas, preventing production of insulin. According to the International Diabetes Federation as of 2015, diabetes affects an estimated 415 million people worldwide, of which 44 million are in North America.

Gu, Buse, and colleagues devised their solution using liposomes, tiny bubbles made from natural oils. In this case, the liposome bubbles are designed with a double layer to keep from releasing their insulin payloads until needed. When glucose levels in blood are normal, both layers of the bubbles remain intact. However, when glucose levels rise, peptides — short protein chains — on the surface of the outer layer react by coiling into the inner membrane of the bubble. The two membrane layers then fuse, releasing the insulin stored in the inner bubble into the blood stream.

The researchers tested their artificial beta cells first in lab cultures and then in mice. The mice, induced with diabetes and lacking beta cells, were given one injection of the artificial cells, and according to Gu in a university statement, “went from hyperglycemic to normoglycemic within an hour, and they remained normoglycemic for up to five days after that.” Similar mice given injections of liposome bubbles without insulin remained with high glucose levels.

The North Carolina team plans to incorporate their discovery into its development of a skin patch to painlessly deliver synthetic beta cells. As reported in Science & Enterprise in June 2015 and March 2016, the researchers designed and tested the patch with about 100 microneedles to deliver its payload, first using insulin and then natural beta cells. The patch’s microneedles puncture the outer layers of skin, which causes no pain, but exposes the contents — artificial beta cells in this case — to capillaries.

“There is still much work needed to optimize this artificial-cell approach before human studies are attempted,” notes Buse, “but these results so far are a remarkable, creative first step to a new way to solve the diabetes problem using chemical engineering as opposed to mechanical pumps or living transplants.”

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