Corresponding author and professor of chemical and biological engineering at the School of Engineering at Tufts University, Emmanuel Tzanakakis, PhD, and colleagues set out to develop a real-time connection between blood-glucose concentration and subsequently triggered release of compensatory insulin. The team reported that light-triggered insulin production was increased up to three times from baseline but only in the presence of elevated blood glucose, observing that insulin production remained appropriately low when blood glucose was low.
“It’s a backwards analogy, but we are actually using light to turn on and off a biological switch,” said Dr. Tzanakakis, who added, “In this way, we can help in a diabetic context to better control and maintain appropriate levels of glucose without pharmacological intervention. 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 [cyclic adenosine monophosphate] transiently in beta cells to get them to make more insulin only when it’s needed.”
Using cultured beta-cells and islets expressing a photoactivatable adenylyl cyclase, researchers established that these cells were responsible for increasing beta-cell insulin production when exposed to blue light. The team transplanted these genetically enhanced cells into mice and demonstrated that they had less hyperglycemia and higher levels of insulin when exposed to this light.
The researchers concluded, “Embedding optogenetic networks in beta-cells for physiologically relevant control of GSIS will enable novel solutions potentially overcoming the shortcomings of current treatments for diabetes.”
According to Fan Zhang, first author of the study and PhD candidate, “There are several advantages to using light to control treatment, obviously, the response is immediate; and despite the increased secretion of insulin, the amount of oxygen consumed by the cells does not change significantly as our study shows. Oxygen starvation is a common problem in studies involving transplanted pancreatic cells.” The team highlights that this light-induced intervention does not share the same shortcomings of current pharmacotherapy and relies on the same physiologic dependence of blood glucose–triggered insulin secretion. The scientists support further research examining photostimulation and optogenetic technology to treat diabetes.
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