Patients with ALS (amyotrophic lateral sclerosis) often suffer from type 2 diabetes. This phenomenon has since long remained mechanistically enigmatic. Now, researchers have identified a molecular mechanism linking these two diseases. The study is published in the scientific journal PNAS.
The researchers found that immunoglobulin G (IgG) antibodies in the blood of ALS patients target the calcium channel in the cell membrane of the insulin-secreting beta cells in the pancreas.
"This leads to an unphysiological calcium (Ca2+) influx and consequent beta cell death," says the first author of the study.
Altered humoral immunity, i.e. the presence of autoantibodies targeting the body's own cells, is a known phenomenon in type 1 diabetes. The new study highlights the presence of autoantibodies as a pathogenic mechanism in a subgroup of patients with type 2 diabetes.
"We now demonstrate that IgG from ALS patients with type 2 diabetes behave like cytotoxic autoantibodies, suggesting that altered humoral immunity can serve as a critical pathogenic mechanism in the development of diabetes," says the senior author of the study. "This may lay the foundation for a new immunotherapy strategy for patients suffering from both ALS and diabetes."
The researchers believe that the presence of autoantibodies may be a generalised phenomenon for other neurodegenerative diseases as well. Similar to ALS patients, a proportion of patients with disorders like Alzheimer's disease, Parkinson's disease and multiple sclerosis also suffer from type 2 diabetes.
"Interestingly, pancreatic beta cells and neurons are equipped with similar types of calcium channels and share a series of physiological and pathological mechanisms for their function/dysfunction and survival/death, such as Ca2+-dependent exocytosis and Ca2+-triggered cell death," says the senior author of the study. "The extent to which the pathogenic mechanism that we discovered in patients with both ALS and type 2 diabetes may be generalised to other neurodegenerative diseases associated with diabetes will be the focus for future studies."
Auto-antibodies may be responsible type 2 diabetes in ALS patients
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