Treating type 1 diabetes and some cases of type 2 diabetes has long required painful and frequent insulin injections or a mechanical insulin pump for insulin infusion. But researchers have now developed what could be a much more patient-friendly option: artificial cells that automatically release insulin into the bloodstream when glucose levels rise.
These "artificial beta cells" (AβCs) 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.
As the researchers report in Nature Chemical Biology, a single injection of the AβCs into diabetic mice lacking beta cells quickly normalized the animals' blood glucose levels and kept those levels normal for up to five days.
"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.
At least six million people in the United States use insulin as a diabetes treatment, either by injection or a mechanical pump. So far, delivered insulin in pill form has been challenging because it's a large molecule that would be destroyed by digestive enzymes and acids before it could reach the bloodstream.
The major problem with current insulin treatments, however, is not that they can't be delivered in a pill, but that they can't control blood glucose levels automatically and efficiently, as normal insulin-secreting pancreatic cells do. Transplants of pancreatic cells can solve that problem in some cases. However, such cell transplants are expensive, require donor cells that are often in short supply, require immune-suppressing drugs, and often fail due to the destruction of the transplanted cells.
TheABCs are constructed with a simplified version of a normal cell's two-layered lipid membrane. The key innovation is what these cells contain: specially designed, insulin-stuffed vesicles. A rise in blood glucose levels leads to chemical changes in the vesicle coating, causing the vesicles to start fusing with the AβC's outer membrane - thus releasing the insulin payloads.
"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'," said the lead author.
The AβCs showed a rapid responsiveness to excess glucose levels in lab-dish tests and in diabetic mice without beta cells. "The mice went from hyperglycemic to normoglycemic within an hour, and they remained normoglycemic for up to five days after that," the lead author said. Control mice injected with no-insulin AβCs remained hyperglycemic.
Researchers plan further preclinical tests and expect to develop a method for delivering the cells painlessly via a skin patch that could be simply replaced.
Artificial beta cells to secrete insulin!
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