Insulin-producing beta cells which can be switched on and off by blue light have been transplanted into mice with diabetes, researchers report.
A team from Tufts University in Massachusetts say the newly engineered cells increased insulin levels by up to three times the amount in the presence of higher glucose levels but not when glucose levels were low. The researchers report that the transplanted cells also led to improved glucose tolerance.
The researchers tested the transplanted cells in mice that had been treated with streptozotocin, a chemical that destroys beta cells. The cells were transplanted under the skin of the mice which allowed for the blue light to better reach the cells.
By using ‘optogenetics’ technology, the researchers found they could control the cells by using blue light. The method involved genetically engineering the beta cells with a gene that codes for an enzyme that allows the beta cells to respond to blue light.
The enzyme the gene encodes is photoactivatable adenylate cyclase (PAC) and this produces the molecule cyclic adenosine monophosphate (cAMP) which activates calcium channels that are involved in the release of insulin by beta cells.
Emmanuel Tzanakakis, professor of chemical and biological engineering at the School of Engineering at Tufts University and corresponding author of the study, said: “The cells do the work of insulin production naturally and the regulatory circuits within them work the same; we just boost the amount of cAMP transiently in beta cells to get them to make more insulin only when it’s needed.”
The transplantation could be useful in people with diabetes that produce too little insulin such as people who have undergone a pancreatectomy that has reduced or prevented insulin production, or in people with type 2 diabetes that have reduced ability to produce sufficient insulin.
The advantage of the blue light technique is that insulin-producing can be turned down when insulin is not needed. This could help to reduce hypoglycemia and unwanted weight gain which can be a feature of treatment with basal insulin.
The technique would have more challenges for use in people with type 1 diabetes as the immune system, in people with type 1, would be able to attack and destroy the transplanted cells. Some research teams are working on ways to prevent the immune system from attacking transplanted beta cells.
The findings have been published in the ACS Synthetic Biology journal.