When people think of the immune system, they picture its role in fighting infections. However, a groundbreaking finding by the Champalimaud Foundation indicates that the immune system functions much broader than this insight and, consequently, could turn on its head the hitherto held view of how the body regulates sugar in conditions of low energy-low or negligible food intake, for instance, during intermittent fasting, exercise, etc.
The study proposes the immune system as a major regulator of blood sugar.
The functions of hormones like insulin and glucagon in blood sugar regulation are well known. Still, the Champalimaud study suggests a surprising new consideration: that immune cells could be a third entity.
According to Henrique Veiga-Fernandes, head of the Immunophysiology Lab at the Champalimaud Foundation, immunology has focused primarily on infection and immunity for years. However, his team’s research reveals that the immune system also plays a crucial role in maintaining blood sugar stability, particularly in times of energy scarcity.
“Our study shows that the immune system acts as a kind of ‘postman,’ helping to regulate glucose by communicating with the nervous and hormonal systems,” Veiga-Fernandes said. This previously unknown collaboration opens new possibilities for managing metabolic disorders like diabetes, obesity, and even cancer.
Veiga-Fernandes and his team studied immune cells known as ILC2, which are important for glucagon production, a hormone that elevates blood sugar. Glucose levels had dropped dangerously low in mice that lacked these immune cells. Transplanting ILC2 cells into these mice restored normal glucose regulation, confirming the immune system’s important role.
Initially, the researchers could not conclude how immune cells contributed to glucagon production. While the liver was considered the primary organ related to glucagon’s effects, the team found that the immune cells were migrating from the intestines to the pancreas and that they stimulated glucagon production.
“We were surprised to find that this process is not just localized in the liver but involves a dynamic interaction between the intestine, pancreas, and immune system,” said Veiga-Fernandes.
The study revealed a dramatic journey of immune cells that surprised even the researchers. After fasting, immune cells traveled from the gut to the pancreas, releasing cytokine signals that prompted the pancreas to produce glucagon. Blocking these cytokines resulted in a significant drop in glucagon levels, underscoring the essential role of immune cells in stabilizing blood sugar.
More remarkable is that any infection does not evoke the migration of these immune cells but is a normal, regulated mechanism directed by the nervous system. In a state of hunger or fasting, the neurons of the gut will signal immune cells to unpack their bags and take a trip out of the intestine on the road to the pancreas. This complex interaction between the nervous and immune systems allows the body to produce glucose on demand, particularly when low energy intake.
The discovery of this intricate neuroimmune-hormonal circuit significantly impacts metabolic health. By understanding how immune cells contribute to blood sugar regulation, researchers hope to tackle global diabetes, which has crippled millions of individuals worldwide.
Additionally, the findings could have significant implications for cancer treatment. Certain cancers, like pancreatic neuroendocrine tumors and liver cancer, hijack the body’s metabolic processes, using glucagon to fuel their growth. Understanding how immune cells influence glucagon production could lead to new therapies for these cancers, as well as for conditions like cachexia, a severe weight loss syndrome associated with cancer.
“The immune system is not just fighting infections. It’s part of a much more complex, integrated system that ensures the body can survive periods of energy shortage,” said Veiga-Fernandes. “By targeting the neuroimmune pathways we’ve uncovered, we could develop new approaches to treating metabolic diseases and cancers that exploit these mechanisms.”
This study represents a significant step forward in understanding how the body maintains balance, especially in times of stress or energy scarcity. It also highlights the complex, interconnected nature of the body’s systems, where the immune system is not just a defender but a key player in maintaining metabolic stability.
As Veiga-Fernandes concludes, “We are only just beginning to understand how these systems communicate with one another. This discovery opens up exciting new possibilities for treatments that could benefit millions of people suffering from conditions like diabetes, obesity, and cancer.”
With this new knowledge, the future of managing these widespread health issues may lie in harnessing the body’s immune and metabolic networks to restore balance and improve patient outcomes.
Journal Reference:
- Marko Sestan, Bruno Raposo et al. Neuronal-ILC2 interactions regulate pancreatic glucagon and glucose homeostasis. Science. DOI: 10.1126/science.adi3624
Source: Tech Explorist
