Researchers at Tufts University (MA, USA) have constructed insulin-producing cells that can respond to light. The pancreatic β cells, designed by Fan Zhang and Emmanuel Tzanakakis (both Tufts University), were transplanted beneath the skin of diabetic mice and showed a two to three times increase in the amount of insulin produced when exposed to light, corresponding to a reduction in hyperglycemia. It is hoped that this new method could lead to a potential therapy for diabetes, a condition which affects 30 million Americans.
Zhang and Tzanakakis engineered the pancreatic β cells to express a photo-activatable adenylate cyclase gene (PAC). Utilizing optogenetics – a field which has recently shown strong advances in utilizing light as a genetic switch within artificial systems – the PAC can respond to blue light, increasing insulin production and causing a decrease in blood sugar levels.
The PAC gene increases the production of cAMP within a cell, an intermediate signaling molecule used by pancreatic cells to regulate their response to blood sugar. Due to the high level of cAMP that is created in the presence of light and high glucose levels, the cells are compelled to produce more insulin, overcoming the low effectiveness of the signal in diabetes. By coupling their light sensitive gene to the normal insulin response system, the researchers hope that the body can regulate the system adequately without constant maintenance, avoiding the peaks and valleys in blood sugar levels associated with current pharmacological approaches.
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 β cells to get them to make more insulin only when it's needed,” explained Tzanakakis.
Diabetes is caused by the inability to respond to insulin and store glucose from the blood, resulting in high blood sugar, and potentially amputations, blindness and a range of other conditions. While there are various forms of the condition, Type 2 diabetes makes up 90% of patients and involves a desensitization to the insulin signal, which researchers hope this new process will overcome.
Following the publication of their findings, the researchers now seek to investigate how these cells could be utilized in the creation of a bioartificial pancreatic device.
Sources: F Zhang, E Tzanakakis. Amelioration of diabetes in a murine model upon transplantation of pancreatic β-cells with optogenetic control of cyclic AMP. ACS Synth Biol. 8(10), 2248–2255 (2019); https://now.tufts.edu/news-releases/researchers-engineer-insulin-producing-cells-activated-light-diabetes
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What is optogenetics?
Optogenetics is the process of utilizing light sources and receptors to control genetic switches. The ability to precisely and remotely transmit light of specific wave lengths to the manipulated cells raises the possibilities of precision manipulations and treatments which would not previously have been possible.
Why does diabetes happen?
There are various forms of diabetes. While some are more obviously genetic, Type 2 diabetes is the most common and is associated with consistently high blood sugar. As blood sugar increases, healthy individuals release insulin to store the excess sugar from the blood; however, cells can become desensitized to insulin with prolonged exposure, leading to high blood sugar levels. Individuals with a family history of diabetes, mental health issues and higher proportions of body fat are often considered at high risk of the condition.