This is one in a series presenting news on technology and innovation, made possible with generous support from the Lemelson Foundation.
During pregnancy, parents love to take a first peek at the baby developing inside mom’s body. Special sound waves, with a frequency too high for the human ear to hear, make this imaging possible. But these ultrasound waves can do much more. Researchers are now exploring whether this type of energy can control diabetes before it damages the body.
In most people with diabetes, the body doesn’t respond normally to the hormone insulin. In some people, the body doesn’t make insulin at all. Insulin’s job is to move a simple sugar (glucose) circulating in our blood into cells throughout the body. Glucose fuels the growth and activity of those cells. If insulin can’t do its job, glucose builds up in the blood. Over time, that can damage organs.
Vesna Zderic is a biomedical engineer at George Washington University. That’s in Washington, D.C. Zderic uses her engineering knowledge to solve medical problems. In one of her projects, she has focused on the cells that make and release insulin. These cells, called beta (Bay-tah) cells, live in the pancreas (PAN-kree-us). This organ, which sits behind the stomach, is about 15 centimeters (6 inches) long.
Other researchers had shown that ultrasound could prompt brain cells to release certain signaling chemicals. Zderic and her colleagues wondered if ultrasound might similarly trigger beta cells to release insulin. Many diabetes drugs affect beta cells this way. But those drugs can be costly, especially for lifelong treatments. And diabetes drugs often have unpleasant side effects.
If ultrasound could trigger beta cells to release insulin, it might halt the common form of diabetes in its tracks. That would be important, Zderic reasoned. People with advanced diabetes can develop serious damage to the heart and kidneys. They may even become blind. At that point, many of their beta cells will have died. Their body will no longer be able to make much insulin, if any.
So Zderic’s team figured out a way to treat cells inside the pancreas with ultrasound. And in new tests, the researchers confirm that the technique works — at least in mice.
“Common diabetes drugs often upset the digestive system or harm the kidneys,” observes Tania Singh. She’s a biomedical engineer who worked in Zderic’s lab as a student. Like her mentor, she hopes the ultrasound treatment might one day offer a way to avoid these drugs’ side effects.
The need to manage glucose
Every time you eat a meal, your digestive system breaks down food into its chemical building blocks. One of these is glucose. Once released in the gut, glucose will travel through the blood to body parts that need energy to function. The heart pumping at 60 beats per minute, for instance, requires a regular supply of energy from food sources.
Throughout the body, cells need to take up glucose to turn its chemical energy into a usable form. The hormone insulin is a glucose sensor. As blood glucose levels rise, insulin acts as a key to unlock the cells and let glucose in. That removes the sugar from the circulating blood.
But that system is broken in diabetes.
In type 1 diabetes, the body’s own immune system kills the insulin-making beta cells. That means the body doesn’t have the key for managing glucose. In type 2 diabetes, the body makes insulin, but cells don’t respond to it as they should. The key is broken.
When the key for removing glucose is missing or broken, sugar levels in the blood will rise to abnormal levels. Very high levels can damage tissues. (Doctors diagnose diabetes when blood glucose levels exceed 125 milligrams per deciliter after fasting. Normal levels are 100 or less.)
Earlier, Zderic’s team had zapped beta cells growing in a dish with a five-minute beam of continuous ultrasound. That boosted the cells’ insulin release. The researchers reported the findings two years ago. Singh tackled the next step: testing to see if beta cells would do the same thing in healthy mice. The team chose this animal because its pancreas is similar to the human organ.
For the test, they treated one group of mice with ultrasound and left a second group untreated. (Such untreated groups are known as controls.) After numbing the mice, Singh measured the insulin levels in each animal’s blood. Then she put both groups of mice on small stretchers and placed an ultrasound probe on their bellies. She then turned on the ultrasound in the treatment group for five minutes. Afterward, she again measured blood insulin levels in both groups.
Treatment upped insulin levels by about 20 percent. That increase was similar to the results for beta cells tested in a dish. At the same time, insulin levels fell in the control animals. The ultrasound increased the temperature of the surrounding tissue. But it didn’t cause any skin burns in the mice. And the pancreas and nearby organs weren’t injured.
Singh described her team’s findings at a meeting of the Acoustical Society of America in May. The meeting took place in Louisville, Ky.
New method needs more testing
These results are intriguing, says Gabriela Da Silva Xavier. She works at the University of Birmingham, in England. There, she studies how diabetes disturbs the normal response of cells to glucose and insulin. Still, as promising as the data appear, Da Silva Xavier thinks the researchers will need to answer many more questions.
For one, beta cells make up only 1 to 2 percent of cells in the pancreas. “It’s really important to check if ultrasound triggers the release of chemicals from any other cells,” Da Silva Xavier says. After all, those other cells perform important tasks. Some digest food. Some produce other hormones.
That release of other chemicals could happen if ultrasound affects the cells’ outer membrane. If the cell were a soap bubble, the membrane would be the soap layer that surrounds the pocket of air. Beta cells may release insulin because the ultrasound vibrations make their membranes leaky. If that happens to membranes of other cells in the pancreas, their contents may spill out, too.
But a different mechanism might also explain the effect of ultrasound on insulin, says Julianna Simon. She is an acoustics expert at Pennsylvania State University, in State College. She was not involved in the project.
“I think the treatment basically massages the pancreas,” she says. “It sends energy, in the form of a pressure wave, into the body.” There, she says, it likely “compresses and expands the tissue.” This pancreas massage might cause the release of insulin without changing the cell membrane.
Zderic’s team is testing several theories for the effect of sound waves on the cells in the pancreas. The researchers also will study how to target only the beta cells. They’ll also gauge how long they need to zap them to lower blood glucose levels.
They plan to test the method repeatedly on mice that are already obese or diabetic. That will better mimic treating people recently diagnosed with diabetes. Next, the researchers hope to study larger animals, such as pigs. If all those tests go well, Zderic’s team may begin safety studies in human volunteers.
What’s the team’s long-term vision? “It may be possible to implant a device on the pancreas that's linked to a blood glucose monitor,” Singh says. “When the sensor detects high glucose levels, the device would apply ultrasound to release insulin. When glucose levels are back to normal, it would stop.”
Says Da Silva Xavier, being able to do that “would be brilliant.”
acoustic Having to do with sound or hearing.
biomedical engineer An expert who uses science and math to find solutions to problems in biology and medicine; for example, they might create medical devices such as artificial knees.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
colleague Someone who works with another; a co-worker or team member.
control A part of an experiment where there is no change from normal conditions. The control is essential to scientific experiments. It shows that any new effect is likely due only to the part of the test that a researcher has altered. For example, if scientists were testing different types of fertilizer in a garden, they would want one section of it to remain unfertilized, as the control. Its area would show how plants in this garden grow under normal conditions. And that gives scientists something against which they can compare their experimental data.
deciliter One-tenth of a liter (equal to 3.4 fluid ounces or 6.7 tablespoons).
develop To emerge or come into being, either naturally or through human intervention, such as by manufacturing. (in biology) To grow as an organism from conception through adulthood, often undergoing changes in chemistry, size and sometimes even shape.
diabetes A disease where the body either makes too little of the hormone insulin (known as type 1 disease) or ignores the presence of too much insulin when it is present (known as type 2 diabetes).
diagnose To analyze clues or symptoms in the search for their cause. The conclusion usually results in a diagnosis — identification of the causal problem or disease.
digest (noun: digestion) To break down food into simple compounds that the body can absorb and use for growth. Some sewage-treatment plants harness microbes to digest — or degrade — wastes so that the breakdown products can be recycled for use elsewhere in the environment.
engineer A person who uses science to solve problems. As a verb, to engineer means to design a device, material or process that will solve some problem or unmet need.
frequency The number of times some periodic phenomenon occurs within a specified time interval. (In physics) The number of wavelengths that occurs over a particular interval of time.
gauge A device to measure the size or volume of something. For instance, tide gauges track the ever-changing height of coastal water levels throughout the day. Or any system or event that can be used to estimate the size or magnitude of something else. (v. to gauge) The act of measuring or estimating the size of something.
glucose A simple sugar that is an important energy source in living organisms. As an energy source moving through the bloodstream, it is known as “blood sugar.” It is half of the molecule that makes up table sugar (also known as sucrose).
gut An informal term for the gastrointestinal tract, especially the intestines.
hormone (in zoology and medicine) A chemical produced in a gland and then carried in the bloodstream to another part of the body. Hormones control many important body activities, such as growth. Hormones act by triggering or regulating chemical reactions in the body.
immune system The collection of cells and their responses that help the body fight off infections and deal with foreign substances that may provoke allergies.
implant A device manufactured to replace a missing biological structure, to support a damaged biological structure, or to enhance an existing biological structure. Examples include artificial hips, knees and teeth; pacemakers; and the insulin pumps used to treat diabetes. Or some device installed surgically into an animal’s body to collect information on the individual (such as its temperature, blood pressure or activity cycle).
insulin A hormone produced in the pancreas (an organ that is part of the digestive system) that helps the body use glucose as fuel.
kidney Each in a pair of organs in mammals that filters blood and produces urine.
mechanism The steps or process by which something happens or “works.” It may be the spring that pops something from one hole into another. It could be the squeezing of the heart muscle that pumps blood throughout the body. It could be the friction (with the road and air) that slows down the speed of a coasting car. Researchers often look for the mechanism behind actions and reactions to understand how something functions.
membrane A barrier which blocks the passage (or flow through) of some materials depending on their size or other features. Membranes are an integral part of filtration systems. Many serve that same function as the outer covering of cells or organs of a body.
mentor An individual who lends his or her experience to advise someone starting out in a field. In science, teachers or researchers often mentor students or younger scientists by helping them to refine their research questions. Mentors also can offer feedback on how young investigators prepare to conduct research or interpret their data.
monitor To test, sample or watch something, especially on a regular or ongoing basis.
obese Extremely overweight. Obesity is associated with a wide range of health problems, including type 2 diabetes and high blood pressure.
organ (in biology) Various parts of an organism that perform one or more particular functions. For instance, an ovary is an organ that makes eggs, the brain is an organ that makes sense of nerve signals and a plant’s roots are organs that take in nutrients and moisture.
pancreas A gland found in animals with backbones that secretes the hormone insulin and enzymes that help break down foods in the gut.
preliminary An early step or stage that precedes something more important.
pressure wave (in geoscience) A type of wave that moves through materials in a manner similar to the movement of sound through air. That is, it jiggles the material back and forth along the same line as the path of the wave. Moreover, unlike other types of seismic waves, these can travel through more than just solids. They also can move through liquids and gases.
sensor A device that picks up information on physical or chemical conditions — such as temperature, barometric pressure, salinity, humidity, pH, light intensity or radiation — and stores or broadcasts that information. Scientists and engineers often rely on sensors to inform them of conditions that may change over time or that exist far from where a researcher can measure them directly. (in biology) The structure that an organism uses to sense attributes of its environment, such as heat, winds, chemicals, moisture, trauma or an attack by predators.
side effects Unintended problems or harm caused by a procedure or treatment.
sound wave A wave that transmits sound. Sound waves have alternating swaths of high and low pressure.
tissue Made of cells, it is any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues.
type 2 diabetes (see also diabetes) A disease caused by the body’s inability to effectively use insulin, a hormone that helps the body process and use sugars. Unless diabetes is controlled, a person faces the risk of heart disease, coma or death.
ultrasound (adj. ultrasonic) Sounds at frequencies above the range that can be detected by the human ear. Also the name given to a medical procedure that uses ultrasound to “see” within the body.
wave A disturbance or variation that travels through space and matter in a regular, oscillating fashion.
Meeting: T. Singh et al. Therapeutic ultrasound-induced insulin release in vivo.177th Meeting of the Acoustical Society of America. May 13-17, 2019. Louisville, Ky.
Journal: I. Suarez Castellanos et al. Ultrasound stimulation of insulin release from pancreatic beta cells as a potential novel treatment for type 2 diabetes. Ultrasound in Medicine & Biology. Vol 43, June 2017, p. 1210. doi: 10.1016/j.ultrasmedbio.2017.01.007.