Researchers develop light-activated insulin-producing cells for diabetes

The researchers caused the beta cells in the artificial pancreas to secrete insulin when exposed to blue light. Insulin is shown here as an atomic model filling the space. Credit: Tufts University

Researchers at Tufts University transplanted beta cells from the modified pancreas into diabetic mice and allowed the cells to produce more than two to three times the typical level of insulin by exposing them to light. Light-switchable cells are designed to compensate for lower insulin production or reduced insulin response in diabetic individuals. The study published in ACS Synthetic Biology shows that glucose levels can be controlled in a mouse model of diabetes without pharmacological intervention.

Insulin is a hormone that plays a central role in the precise control of circulating glucose levels, the essential fuel used by cells. Diabetes affects more than 30 million Americans according to the Centers for Disease Control and Prevention (CDC). In type II diabetes - the most common form of the disease - the body's cells react ineffectively with insulin and, as a result, the circulating glucose can become dangerously high (hyperglycemia) while the pancreas can not not produce enough insulin to compensate. In type I diabetes, beta cells, which are the only insulin-producing cells in the body, are destroyed by the immune system, resulting in a complete absence of the hormone.

Current treatments include the administration of drugs that enhance insulin production by pancreatic beta cells, or direct injection of insulin to supplement the natural supply. In both cases, the regulation of blood glucose becomes a manual process, the intervention of a drug or insulin being performed after periodic readings of blood glucose, often leading to spikes and troughs that can have adverse effects long-term.

The researchers sought to develop a new way to boost insulin production while maintaining the important real-time link between insulin release and glucose concentration in the blood. They did this by taking advantage of optogenetics, a protein-based approach that modifies their on-demand activity with light. The pancreatic beta cells have been modified with a gene that encodes a photoactivatable adenylate cyclase enzyme (PAC). PAC produces cyclic adenosine monophosphate (cAMP) when exposed to blue light, which increases the production of glucose-stimulated insulin in the beta cell. Insulin production can increase two to three times, but only when the amount of blood glucose is high. When blood glucose is low, insulin production remains low. This avoids the common disadvantages of diabetes treatments, which can overcompensate insulin exposure and leave the patient with a harmful or dangerously low blood sugar level (hypoglycaemia).

The researchers found that transplanting artificial pancreatic beta cells into the skin of diabetic mice improved tolerance and glucose regulation, reduced hyperglycemia, and increased plasma insulin levels during blue light illumination.

"It's a retrograde analogy, but we actually use light to activate and deactivate a biological switch," said Emmanuel Tzanakakis, professor of chemical and biological engineering at the School of Engineering at Tufts University and corresponding author of the 'study. "In this way, we can help, in the diabetic context, to better control and maintain the appropriate glucose levels without pharmacological intervention.The cells naturally perform the work of insulin production and the regulatory circuits within them work from the In the same way, we simply increase the amount of transient cAMP in beta cells to produce more insulin than is needed. "

Blue light simply switches the switch from normal mode to fast mode. Such optogenetic approaches using light-activatable proteins to modulate cell function are being explored in many biological systems and have fueled efforts to develop a new kind of treatment.

"The use of light to control treatment has several advantages," said Fan Zhang, a graduate student at Tzanakakis Lab in Tufts and the first author of the study. "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 deficiency is a common problem in studies involving transplanted pancreatic cells. "


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