People with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases have an increased risk of developing type 2 diabetes. Now researchers have identified a possible biological mechanism.
People with ALS often have type 2 diabetes, although ALS is neurodegenerative and type 2 diabetes is metabolic.
Researchers at Karolinska Institutet have identified a molecular mechanism for the link between these diseases.
The new research shows that antibodies in the blood of people with ALS target the insulin-secreting beta cells in the pancreas, and destroying these leads to type 2 diabetes.
“The discovery may lay the foundation for a pharmaceutical treatment strategy for people with both ALS and diabetes ,” explains Per-Olof Berggren, Professor and Director, Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
The study was recently published in the Proceedings of the National Academy of Sciences of the United States of America.
ALS makes the immune system attack the pancreas
The link between ALS and type 2 diabetes results from autoantibodies that attack the body’s own cells and, among people with ALS, the nerve cells in the brain.
The new study shows that something similar occurs when ALS leads to the development of type 2 diabetes.
The new research shows that immunoglobulin G (IgG) antibodies in the blood of people with ALS target the calcium channels in the cell membranes of the insulin-secreting beta cells in the pancreas.
Impairing the calcium channels enables calcium to flow freely into the beta cells and causes cell death.
“This suggests that ALS altering immunity can be a pathogenic mechanism in developing type 2 diabetes,” explains Per-Olof Berggren.
May also apply to other diseases
The researchers believe that autoantibodies may generally be present in other neurodegenerative diseases.
Similar to people with ALS, many people with such diseases as Alzheimer’s, Parkinson’s and multiple sclerosis have type 2 diabetes.
Per-Olof Berggren explains that 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 or dysfunction.
“Future studies will focus on the extent to which the pathogenic mechanism we discovered in people with both ALS and type 2 diabetes may be generalized to other neurodegenerative diseases associated with diabetes,” says Per-Olof Berggren.
Immune cells from people with ALS destroyed mouse pancreas cells
In attempting to demonstrate this mechanism, the researchers purified the IgG from people with both ALS and type 2 diabetes.
They then applied this IgG to mouse pancreas and examined how its cells reacted.
The IgG caused the calcium channels in the pancreas cells to absorb more calcium, but also affected the mitochondria, which act as the cell’s power plants.
In addition, the experiments showed that insulin secretion and cell viability were impaired.
“The results show that serum from people with both ALS and type 2 diabetes interferes with cell survival through a mechanism involving IgG and calcium channels. This occurs by enhancing the influx of calcium into the cells, resulting in impaired mitochondrial function,” says Per-Olof Berggren.
“IgGs from patients with amyotrophic lateral sclerosis and diabetes target CaVα2δ1 subunits impairing islet cell function and survival” has been published in the Proceedings of the National Academy of Sciences of the United States of America. In 2018, the Novo Nordisk Foundation awarded a grant to Per-Olof Berggren for the project Reporter Islets in the Eye as a Personalized-medicine Readout for Diabetes.