Caption: Artificial beta cell, made of a lipid bubble (purple) carrying smaller, insulin-filled vesicles (green). Imaged with cryo-scanning electron microscope (cryo-SEM) and colorized. Credit: Zhen Gu Lab
People with diabetes have benefited tremendously from advances in monitoring and controlling blood sugar, but they’re still waiting and hoping for a cure. Some of the most exciting possibilities aim to replace the function of the insulin-secreting pancreatic beta cells that is deficient in diabetes. The latest strategy of this kind is called AβCs, short for artificial beta cells.
As you see in the cryo-SEM image above, AβCs are specially designed lipid bubbles, each of which contains hundreds of smaller, ball-like vesicles filled with insulin. The AβCs are engineered to “sense” a rise in blood glucose, triggering biochemical changes in the vesicle and the automatic release of some of its insulin load until blood glucose levels return to normal.
In recent studies of mice with type 1 diabetes, researchers partially supported by NIH found that a single injection of AβCs under the skin could control blood glucose levels for up to five days. With additional optimization and testing, the hope is that people with diabetes may someday be able to receive AβCs through patches that painlessly stick on their skin.
Caption: Insulin-containing pancreatic beta cells (green) derived from human stem cells. The red cells are producing another metabolic hormone, glucagon, that regulates blood glucose levels. Blue indicates cell nuclei. Credit: The Salk Institute for Biological Studies, La Jolla, CA
In people with type 1 diabetes, the immune system kills off insulin-producing beta cells of the pancreas needed to control the amount of glucose in their bloodstream. As a result, they must monitor their blood glucose often and take replacement doses of insulin to keep it under control. Transplantation of donated pancreatic islets—tissue that contains beta cells—holds some promise as a therapy or even a cure for type 1 diabetes. However, such donor islets are in notoriously short supply . Recent advances in stem cell research have raised hopes of one day generating an essentially unlimited supply of replacement beta cells perfectly matched to the patient to avoid transplant rejection.
A couple of years ago, researchers took a major step toward this goal by coaxing induced pluripotent stem cells (iPSCs), which are made from mature human cells, to differentiate into cells that closely resembled beta cells. But a few things were troublesome. The process was long and difficult, and the iPSC-derived cells were not quite as good at sensing glucose and secreting insulin as cells in a healthy person. They also looked and, in some ways, acted like beta cells, but were unable to mature fully in the lab. Now, an NIH-funded team has succeeded in finding an additional switch that enables iPSC-derived beta cells to mature and produce insulin in a dish—a significant step toward moving this work closer to the clinical applications that many diabetics have wanted.
Modeled after Time’s Person of the Year, the journal Science has a tradition of honoring the year’s most groundbreaking research advances. For 2014, the European Space Agency nabbed first place with the Rosetta spacecraft’s amazing landing on a comet. But biomedical science also was well represented on the “Top 10” list—with NIH helping to support at least four of the advances. So, while I’ve highlighted some of these in the past, I can’t think of a better way for the NIH Director to ring in the New Year than to take a brief look back at these remarkable achievements!
Youth serum for real?Spanish explorer Ponce de Leon may have never discovered the Fountain of Youth, but researchers have engineered an exciting new lead. Researchers fused the circulatory systems of young and old mice to create a shared blood supply. In the old mice, the young blood triggered new muscle and more neural connections, and follow-up studies revealed that their memory formation improved. The researchers discovered that a gene called Creb prompts the rejuvenation. Block the protein produced by Creb, and the young blood loses its anti-aging magic . Another team discovered that a factor called GDF11 increased the number of neural stem cells and stimulated the growth of new blood vessels in the brains of older animals .
Caption: Insulin-producing pancreatic beta cells (green) derived from human embryonic stem cells that have formed islet-like clusters in a mouse. The red cells are producing another metabolic hormone, glucagon, that regulates blood glucose levels. Blue indicates cell nuclei. Credit: Photo by B. D. Colen/Harvard Staff; Image courtesy of Doug Melton
For most of the estimated 1 to 3 million Americans living with type 1 diabetes, every day brings multiple fingerpricks to manage their blood glucose levels with replacement insulin [1,2]. The reason is that their own immune systems have somehow engaged in friendly fire on small, but vital, clusters of cells in the pancreas known as the islets—which harbor the so-called “beta cells” that make insulin. So, it’s no surprise that researchers seeking ways to help people with type 1 diabetes have spent decades trying a find a reliable way to replace these islets.
Islet replacement has proven to be an extremely difficult research challenge for a variety of reasons, but exciting opportunities are now on the horizon. Notably, a team of researchers, led by Douglas Melton of Harvard University, Cambridge, MA, and partially funded by NIH, reported groundbreaking success just last week in spurring a human embryonic stem cell (hESC) line and two human-induced pluripotent stem (iPS) cell lines to differentiate into the crucial, insulin-producing beta cells. Not only did cells generated from all three of these lines look like human pancreatic beta cells, they functioned like bona fide, glucose-responsive beta cells in a mouse model of type 1 diabetes .
Caption: Boston University researcher Ed Damiano with his son David, who has type 1 diabetes, in 2002. Credit: Toby Milgrome
From taking selfies to playing Candy Crush, smart phones are being put to a lot of entertaining uses. But today I’d like to share an exciting new use of mobile health (mHealth) technology that may help to save lives and reduce disability among people with type 1 diabetes—an advance inspired by one researcher’s desire to help his son.
By teaming a smart phone with a continuous glucose monitor and two pumps designed to deliver precise doses of hormones, a team from Boston has created a bionic pancreas that appears to control blood glucose levels in people with type 1 diabetes more effectively than current methods. That is a significant achievement because if blood glucose levels are either too high or too low, there can be serious health consequences.
In a healthy body, the pancreas masterfully regulates blood glucose levels by orchestrating the secretion of insulin and another hormone, called glucagon, which raises blood glucose. These hormones work together like an automatic thermostat, raising and lowering blood glucose when appropriate. However, in type 1 diabetes, the pancreas produces little or no insulin, leading to increased levels of glucose that gradually damage blood vessels, kidneys, and nerves, raising the risk of blindness and amputations.