Glucose-Sensing Neurons Promote Blood Glucose Balance
In animal models, the contribution of specific glucose-sensing neurons to the maintenance of blood glucose equilibrium has been studied ().
What are Glucose-Sensing Neurons
"There are many glucose-sensing neurons in the brain that are thought to actively participate in detecting small changes of glucose levels in the body and then trigger responses accordingly to return the level to a healthy range," said Dr. Yong Xu, professor of pediatrics - nutrition, molecular and cellular biology, and medicine at Baylor. "But there have been several questions about this for a long time."
The accepted concept is that blood glucose levels are tightly controlled by hormones secreted in the pancreas, such as insulin and glucagon. So, some scientists have wondered, do glucose-sensing neurons in the brain really play a role in the regulation of whole-body glucose level?
‘Glucose-sensing neurons in the brain are key for regulating glucose levels throughout the entire body. GI neurons play a critical role in diabetes, where pancreatic beta cells fail to produce sufficient insulin to regulate blood sugar levels effectively. #diabetes #bloodglucose’
"Glucose-sensing neurons can be divided into two groups according to how they respond to glucose fluctuations," Xu explained. "One group is called glucose-excited (GE) neurons and the other is the glucose-inhibited (GI) neurons. In this study, we focused on the second group, the less studied of the two."
Different Types of Glucose-Sensing Neurons
Glucose-excited (GE) neurons are activated or excited when the glucose level around them is higher. "This is expected because glucose is a fuel for most cells, including neurons," Xu said. "Having more fuel available would support increased cell activity."On the other hand, GI neurons are inhibited when glucose levels are higher and paradoxically, they are activated when glucose levels are lower. "This has been puzzling to researchers, as they were expecting the opposite, less neuronal activity when glucose is low," Xu said.
The researchers focused on GI neurons located in a region called the ventromedial hypothalamic nucleus (VMH) in the mouse brain. Specifically, they studied which ion channels on GI neurons mediated low-glucose sensing. Ion channels are proteins on the surface of neurons that allow charged ions to flow in and out of the cell. This process is necessary for neuronal activation or firing.
"In fact, our data shows that ano4 is a marker defining GI neurons. If a VMH neuron expresses ano4, then it is a GI neuron. If a VMH neuron does not express ano4, it is not a GI neuron."
The researchers aimed to clarify the underlying mechanism that triggers glucose-inhibited (GI) neuronal activity in response to low glucose levels and evaluate its influence on the regulation of blood glucose.
GI Neurons and Type 1 Diabetes
Next, the researchers investigated the role of GI neurons in the regulation of blood glucose in a mouse model of type 1 diabetes. In this model, insulin-producing pancreatic beta cells are absent. The lack of insulin triggers increased blood sugar levels, the hallmark of diabetes. By genetically eliminating the ano4 gene in the GI neurons located in the VMH in these diabetic mice, the researchers substantially normalized blood sugar levels."In this case, blood glucose levels can be manipulated quite effectively in the mouse model by knocking out a single gene in GI neurons, a small group of cells in the brain. Next, we want to determine whether pharmacological inhibition of ano4 would also help control blood glucose levels in this model of type 1 diabetes, and in models of type 2 diabetes."
References:
- Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia - (https:www.jci.org/articles/view/163391)