Cecilia Lee

Yale researchers are exploring the efficacy of an ultrasound treatment that could regulate blood glucose levels for patients with Type II diabetes.

The Yale scientists are participating in a clinical trial led by GE Research. Raimund Herzog, an assistant professor of endocrinology at the Yale School of Medicine and one of the researchers, explained that the main issue with patients who have Type II diabetes is insulin resistance. Normally, when a person eats, their body releases insulin, which acts as a signal for cells to take up the glucose in the bloodstream. In patients with Type II diabetes, their bodies stop listening to this insulin signal, leading to high levels of blood sugar because cells do not take up the glucose in the bloodstream. This experimental technique aims to target the signaling pathway responsible for regulating glucose uptake through ultrasound treatments. According to a paper published on March 31, scientists were able to lower glucose levels in diabetic rats using this treatment.

“Usually, we think of glucose metabolism as being regulated predominantly by hormones, of which the most important is insulin,” Herzog said. “Over the last couple of years, it has become clear that the nervous system also plays a role in regulating glucose metabolism … In fact, the hypothalamus has emerged as one of the main regulating centers for glucose metabolism.”

Herzog went on to explain that glucose metabolism regulation, meaning how much glucose a person’s cells can take up, is influenced by peripheral nervous system inputs. Specific nerves deliver information from the peripheral nervous system — for example, from the digestive tract — to the hypothalamus. Examples of the information from the peripheral nervous system include when the person in question last ate and whether they live an active lifestyle. 

All of the information gathered by the peripheral nervous system is coordinated by the brain and used to decide how much glucose to store or use, thereby affecting glucose uptake of cells. In a published paper, researchers target the nerves responsible for transmitting this peripheral information to the brain using ultrasound treatments. 

“We’ve known that these nerves are there,” Herzog said. “Now, we can test what happens when we selectively stimulate or block them. This is called neuromodulation, modulating the activity of certain nerve fibers that transmit information about nutrition.”

The goal of the study is to alter the nerve activity that is responsible for sensing the availability of glucose in the body. Researchers specifically targeted the liver because it is an organ that acts as a storage unit for glucose while also being connected to the brain through peripheral nerve fibers, according to Herzog. 

The general idea is to change the information going to the brain about the incoming nutrients, thereby changing the activity levels of neurons in the hypothalamus. In fact, the results in the paper show that certain neurons that respond only to changes in glucose levels, called glucose-excited neurons, exhibited different firing patterns after ultrasound treatment. 

This particular project began when GE Research, the research and development division of the General Electric corporation, conducted a study on the effects of ultrasound on the spleen. During those studies, they used the liver as a control tissue. When they applied ultrasound to the liver, the researchers at GE noticed changes in blood sugar and reached out to Raimund Herzog, a specialist in neuronal regulation of metabolism. 

“The use of ultrasound could be a game-changer in how bioelectronic medicines are used and applied to disease, such as Type-2 diabetes, in the future,” Christopher Puleo, a senior biomedical engineer at GE Research who co-led the study and is an author of the article published in Nature, wrote to the News. “Non-pharmaceutical and device-based methods to augment or replace the current drug-treatments may add a new therapeutic choice for physicians and patients in the future.”

At the moment, Herzog and GE Research are conducting clinical trials to test the efficacy of this ultrasound technique in pre-diabetic and diabetic patients. 

The animal experiments in the published article suggest that the effects of the ultrasound treatment are not acute, but rather linger after the ultrasound treatment. However, researchers have yet to determine how long the effects of the ultrasound treatment last in human patients. 

Approximately 90 to 95 percent of American adults with diabetes suffer from Type II diabetes, according to the CDC. 

SELIN NALBANTOGLU
Selin Nalbantoglu covers breakthrough research for SciTech. She is a first-year in Saybrook College.