“Smart” Synthetic Beta Cells That Automatically Release 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.
Further, for many who suffer from diabetes, insulin injections can be a painful and ‘imprecise’ process of keeping their blood sugar levels under control.
Scientists at University of North Carolina and NC State are developing what they hope will be a less painful, more convenient alternative: “smart” artificial beta cells that can detect the need for insulin and secrete it automatically.
These “artificial beta cells” (ABCs) mimic the functions of the body’s natural glucose-controllers, the insulin-secreting beta cells of the pancreas. The loss or dysfunction of these cells
causes type 1 diabetes and many cases of type 2 diabetes. The idea is that the AβCs could be subcutaneously inserted into patients, which would be replaced every few days, or by a painless and disposable skin patch.“Our plan now is to further optimize and test these synthetic cells in larger animals, develop a skin patch delivery system for them, and ultimately test them in people with diabetes,” said principal investigator Zhen Gu, PhD, a professor in the Joint UNC/NC State Department of Biomedical Engineering. Gu also holds appointments in the UNC School of Medicine, the UNC Eshelman School of Pharmacy, and the UNC Diabetes Care Center.
The study was conducted in mice, by injecting a single dose of AβCs into diabetic mice which lacked beta cells, quickly normalized the blood glucose levels and the levels were normal up to 5 days. Almost 6 million people in the US use insulin for diabetic treatment either by injection or a mechanical pump. Insulin in pill form has been challenging as it’s a large molecule and can easily be destroyed by digestive enzymes and acid before it reaches the bloodstream. Pancreatic cell transplantation can solve the problem in some cases but they are expensive and even require donor cells which are often in short supply.
Biomedical engineering professor Zhen Gu and endocrinologist John Buse 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.
Zhaowei Chen, lead author said, “This is the first demonstration using such a vesicle fusion process for delivering insulin that employs insulin-containing vesicles like those found in a beta cell and can reproduce the beta cell’s functions in sensing glucose and responding with insulin ‘secretion’.”
John Buse, co-author said, “There is still much work needed to optimize this artificial-cell approach before human studies are attempted, 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.”
