Scientists Implant ‘Engineered’ Beta Genes to Produce Insulin
Researchers at the US Tufts University have engineered pancreatic beta cells that could be implanted under the skin, and controlled by light, to fabricate two to three times the regular level of the hormone, and compensate for the lower production or reduced insulin response found in diabetic individuals.
Insulin is a hormone that plays a central role in precisely controlling levels of circulating glucose, the essential fuel used by cells.
In type II diabetes, the most common form of the disease, the cells of the body become inefficient at responding to insulin and as a consequence, glucose in circulation can become dangerously high (hyperglycemia) while the pancreas cannot produce enough insulin to compensate.
In type I diabetes, the beta cells, which are the only cells in the body that produce insulin, are destroyed by the immune system resulting in complete lack of the hormone.
Current treatments include the administration of drugs that enhance the production of insulin by pancreatic beta cells, or direct injection of insulin to supplement the naturally produced supply. In both cases, regulation of blood glucose becomes a manual process, with drug or insulin intervention conducted after periodic readings of glucose levels.
The new method, announced recently in the ACS Synthetic Biology journal, replaces the current treatment, by amplifying insulin production while maintaining the important real-time link between the release of insulin and concentration of glucose in the bloodstream.
The researchers accomplished this by taking advantage of “optogenetics”, an approach relying on proteins that change their activity on demand with light, and can be used to stimulate neurons.
With the help of optogenetics, pancreatic beta cells were engineered with a gene that encodes a photoactivatable adenylate cyclase (PAC) enzyme. The PAC produces the molecule cyclic adenosine monophosphate (cAMP) when exposed to blue light, which in turn cranks up the glucose-stimulated production of insulin in the beta cell.
Insulin production can increase two- to three-fold, but only when the blood glucose amount is high. At low levels of glucose, insulin production remains low. This avoids a common drawback of diabetes treatments which can overcompensate on insulin exposure and leave the patient with harmful or dangerously low blood sugar (hypoglycemia).
Researchers found that transplanting the engineered pancreatic beta cells under the skin of diabetic mice led to improved tolerance and regulation of glucose, reduced hyperglycemia, and higher levels of plasma insulin when subjected to illumination with blue light.
In a report published Saturday by the university's website, Emmanuel Tzanakakis, professor of chemical and biological engineering at Tufts University and corresponding author of the study, said: "The engineered 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.”