Scientists have developed a microfluidic platform that allows the direct visualization of how living insulin-producing islet cells in the pancreas respond to different concentrations of glucose and fatty acids. The technology, which uses no probes or fluorescent tags, has been devised by researchers at the Toronto General Research Institute (TGRI), who hope it could provide new insights into the role that excess nutrients play in causing islet cell dysfunction and type 2 diabetes.
A chronic excess in sugar and fats in the diet is thought to play a key role in causing beta-cell dysfunction and type 2 diabetes by a process known as glucolipotoxicity. In order to study the metabolism of these nutrients directly, the TGRI researchers have developed a platform developed that involves trapping islet tissues in a dam within the microfluidic device, and then passing solutions containing different concentrations of fatty acids and glucose over them. The stationary cells are imaged to detect autofluorescence given off by mitochondrial proteins as a result of changes in metabolic processes that are triggered by the different concentrations of nutrients.
Initial results by Jonathan Rocheleau, Ph.D., and colleagues showed that increasing the concentration of sugar in the system caused a reduction of fat metabolism within minutes. “We’ve created a new opportunity for tissue studies,” Dr. Rocheleau remarks. “Using our techniques, we’re looking at metabolism as it occurs and as naturally as possible ... The beta cell is exquisitely sensitive to glucose even with the availability of other nutrients; inreasing the time to turn off fat metabolism is critical to beta cell survival and a potential target for future therapies.”
The TGRI researchers report on their iplatform in Integrative Biology, in a paper titled “Quantitative imaging of electron transfer flavoprotein autofluorescence reveals the dynamics of liquid partitioning in living pancreatic islets.”