Researchers say they now have a 3-D image of how insulin communicates with cells. They hope this will lead to better synthetic insulin.
Insulin is often referred to as one of the most powerful hormones in the human body. Without it, the human body simply can’t function.
Too little or too much insulin can result in high or low blood glucose (sugar) levels, respectively.
That can be devastating to one’s ability to perform even the simplest tasks, physically or mentally.
Despite having a dozen options of synthetic insulin in today’s pharmaceutical market, people with type 1 or type 2 diabetes still face a daily number of challenges, as manufactured insulin pales in comparison to pancreas-produced insulin.
Researchers, however, hope a recent discovery will eventually improve the function of synthetic insulin.
Through the combined work of structural and cell biology experts along with cryo-electron microscopy specialists and an insulin receptor specialist, the first 3-D image of precisely how insulin communicates with cells in the body was produced. It was recently
“Current insulin therapies are suboptimal, because they have been designed without this missing piece of the puzzle,” explained Mike Lawrence, associate professor at the Walter & Eliza Hall Institute of Medical Research in Australia and an author of the study.
“Together with our collaborators in Germany, we have produced the first definitive 3-D image of the way in which insulin binds to the surface of cells in order to successfully transmit the vital instructions needed for taking up sugar from the blood,” he said.
Lawrence adds that while it’s been long understood that insulin signals to cells to lower blood glucose levels by binding to a receptor, what was actually happening during that interaction was unknown.
Funded in part by the Australian National Health and Medical Research Council, this research and resulting 3-D images demonstrates exactly how insulin triggers cells in the bloodstream to lower blood sugar levels.
In addition to researchers from the Walter & Eliza Hall Institute of Medical Research, other parts of this research team included the pharmaceutical company Sanofi-Aventis Deutschland GmbH and the European Molecular Biology Laboratory (EMBL), both located in Germany.
“We had never before seen the detailed changes that occurred in the receptor itself, confirming that insulin had successfully delivered the message for the cell to take up sugar from the blood,” Lawrence said.
“My colleagues at the institute carefully engineered individual samples of insulin bound to receptors so that our collaborators in Heidelberg could use cryo-electron microscopy to capture hundreds of thousands of high-resolution ‘snapshots’ of these samples,” he added.
Researchers then combined 700,000 two-dimensional snapshots to create a three-dimensional image that precisely illustrated what it looks like when insulin binds to a receptor.
“It was at that point we knew we had the information needed to develop improved insulin therapies that could ensure cells would respond correctly and carry out the functions necessary to lower blood sugar levels,” Lawrence said.
The hope is this discovery will enable pharmaceutical companies to improve the way synthetic insulin currently functions within the body.
That ideally would reduce the chances of low and high blood sugar levels, enabling synthetic insulin to function more like the insulin produced by the pancreas in a person without diabetes.
One of the greatest challenges any person with diabetes taking insulin faces is that even just a half unit more than is needed can result in hypoglycemia, or low blood sugar.
Determining how much insulin to take and when to take it is a complicated estimate. It’s based on carbohydrates, fat, protein, exercise, stress, and how it might contribute to any insulin still active in their bloodstream from the most recent insulin injection.
Variables — including activity, stress, menstrual cycles, adrenaline, caffeine, and some medications (like steroids) — quickly affect insulin needs. But today’s current insulin offerings don’t work quickly or precisely enough to easily compensate for these daily variables.
Will this new understanding of exactly how insulin triggers cells to react and lower blood sugar lead to the development of better insulin therapies for people with diabetes?
Some experts are skeptical.
“This type of discovery adds to the body of knowledge on how insulin works,” Gary Scheiner, MS, CDE, certified diabetes educator and author of the book “Think Like a Pancreas,” told Healthline. “Combined with other research, it can lead to a greater understanding of the mechanics behind diabetes.”
But Scheiner, who’s lived with type 1 diabetes for more than 30 years, doubts this research alone will vastly change today’s manufactured insulin options.
“It is a bit of a leap to say that this will lead to better therapies, at least in the short term,” he said. “We still have to deliver the right amounts of insulin at the right times to the right tissues in order to effectively manage glucose levels… and that’s another story entirely.”
Existing research focused on “glucose-responsive” or “smart” insulin has finally gained momentum and funding in the pharmaceutical world, according to Healthline’s DiabetesMine.
“Smart” insulin would ideally only activate and lower blood sugar when triggered by rising blood sugar, hopefully preventing the risk of hypoglycemic events.
However, the world’s pharmaceutical giants, including Novo Nordisk, Merck, Sanofi, and Eli Lilly and Company, are far from conducting human trials or submitting a product to the U.S. Food and Drug Administration (FDA).
Nonetheless, Lawrence is confident his recent research will significantly help the future’s manufactured insulin, enabling it to more closely mimic the human body’s insulin.
“Going forward, pharmaceutical companies will be able to use our data as a ‘blueprint’ for designing therapies that optimize the body’s uptake of insulin,” he said.