How are diabetes and the immune system connected?

Colin Anderson and Sue Tsai discussed the link between the immune system and diabetes Alberta Diabetes Institute (ADI) series of webinars in celebration of the 100th anniversary of insulin discovery.

November is National Diabetes Awareness Month! As part of the celebrations, we're revisiting five great stories showcasing the breadth of work being done at the University of Alberta in the journey towards a cure. The following story was originally published May 31, 2021

The Alberta Diabetes Institute (ADI) series of webinars in celebration of the 100th anniversary of insulin discovery continued with presentations by ADI members and experts in immunology, Colin Anderson and Sue Tsai, who discussed the link between the immune system and diabetes. According to the researchers, the immune system plays a unique, albeit different role in both Type 1 diabetes (T1D) and Type 2 diabetes (T2D). In T1D the immune system is linked to an autoimmune attack to the pancreas, while in T2D it is associated with obesity and an inflammatory process, with insulin modulating immune responses.

Here are several key takeaways from the webinar.

The complex nature of T1D

Many processes are responsible for building self tolerance and preventing the immune system from attacking one's own bodys (autoimmune response). If one or more of these mechanisms are disrupted, an autoimmune disease—such as T1D—develops. Despite enhanced knowledge about the relationship between the immune system and T1D, not much has changed since 100 years ago in the way the disease is treated. This is because of the complex nature of T1D, which involves multiples inherited (genetic) and environmental factors.

Depleting pancreatic activated immune cells to prevent systemic immunosuppression

Several immune interventions have shown potential to delay the progression of T1D, some of which have gone to clinical trials. None of them have yet been able to prevent the eventual development of the disease. Researchers have found that whole body immunomodulation increases the risks for toxicity and immunosuppression. Therefore, current research is targeting specific immune T-cells in the pancreas, the site of T1D development. When a low dose of multiple antibodies against activated T-cells is delivered directly into the pancreas, these cells are selectively killed and the systemic immune system is protected. 

Obesity and the risk for infections

Insulin is a hormone secreted by the pancreas that controls many metabolic processes. T2D is often associated with insulin resistance and obesity. The latter is well-known to increase the risk for and the severity of certain diseases, such as respiratory tract infections, influenza and COVID-19. Many cells express on their surface receptors for insulin, and dysregulation of these receptors causes metabolic complications, such as insulin resistance. Investigations are underway to clarify the link between disease severity in obesity and impaired response to insulin by immune cells. 

Boosting immune responses via insulin signalling

Researchers have found that T-cells taken from obese models have impaired immunological response against infections and blunted response to insulin. Recent findings show that insulin acts via its receptor on immune cells to boost the response against a viral infection and also that insulin modulates immune cell function. The general theory is that in healthy conditions, during an infection the transient whole body insulin resistance induces the production of more insulin, which boosts the immune response. On the other hand, in obesity, insulin production is already increased before an infection and when more insulin is necessary to boost the immune response the pancreas cannot attend to this need, adding to the severity of the infection.