A groundbreaking study published today in the Journal of Clinical Investigation suggests that targeting specific neurons in the brain, rather than focusing solely on obesity or insulin resistance, could be a key strategy in treating type 2 diabetes.
Researchers from the University of Washington School of Medicine have discovered that AgRP neurons, a subset of cells in the hypothalamus, play a significant role in regulating blood sugar levels in diabetic mice. These neurons have long been known to be hyperactive in diabetes, and their impact on glucose metabolism is now coming into clearer focus.
Dr. Michael Schwartz, an endocrinologist at UW Medicine and the study’s corresponding author, emphasized the importance of these neurons in the development of hyperglycemia. “These neurons are playing an outsized role in hyperglycemia and type 2 diabetes,” Schwartz said.
To investigate their role in diabetes, the research team used a viral genetics technique to introduce tetanus toxin into the AgRP neurons. This toxin blocks communication between the neurons, effectively silencing them. Remarkably, this intervention normalized blood sugar levels in diabetic mice for months, without affecting their body weight or food intake.
Traditionally, type 2 diabetes has been understood as a condition driven by genetic factors and lifestyle issues such as obesity, poor diet, and lack of exercise, leading to insulin resistance or inadequate insulin production. For years, the brain’s involvement in the disease was largely dismissed. However, this new study challenges that notion.
“This paper represents a departure from the conventional wisdom of what causes diabetes,” Schwartz explained, noting that the findings support previous research in which injecting a peptide called FGF1 directly into the brain also led to diabetes remission in mice. This effect was shown to involve long-term suppression of AgRP neurons.
The researchers’ findings suggest that while AgRP neurons play a crucial role in controlling blood sugar, they are not primarily responsible for obesity in these animals. As such, targeting these neurons could potentially help manage diabetes without necessarily reversing obesity.
Dr. Schwartz cautioned that further research is needed to fully understand how AgRP neurons become hyperactive in diabetes and how to effectively regulate their activity. Once these questions are addressed, it could pave the way for novel therapies aimed at taming these neurons to manage blood sugar levels.
This research may also change the way clinicians view and treat type 2 diabetes. Schwartz noted that current diabetes medications, such as Ozempic, already have an effect on AgRP neurons, although the exact contribution of this action to their therapeutic effects remains unclear.
In the future, a deeper understanding of how AgRP neurons control blood sugar could lead to more targeted treatments, potentially offering a breakthrough in the fight against type 2 diabetes.
Related topics:
Obesity and Type 2 Diabetes: Understanding the True Link
