A newly discovered receptor could in the future provide a starting point for treating the cause of diabetes. This docking point, known for short as “Inceptor”, sits on the insulin-producing beta cells of the pancreas and shields them from the blood sugar hormone. It thus contributes to the regulation of insulin production, but can also block it in diabetes. Researchers have now found a way to specifically inhibit this receptor in mice and thus stimulate insulin production again. If this is confirmed, it could make new drugs for diabetes possible.
Around seven million people in Germany suffer from diabetes mellitus. Depending on the type, the disease is caused by the loss or malfunction of the insulin-producing beta cells in the pancreas or by the body cells no longer responding adequately to insulin. As a result, the blood sugar level is chronically increased, which leads to metabolic disorders and, in the long term, multiple organ damage. The disease cannot yet be treated causally. In order to keep their blood sugar level under control, people with severe diabetes need regular injections of insulin.
Fight the cause of diabetes
A team led by Ansarullah from the Helmholtz Zentrum München conducts basic research aimed at combating the molecular causes of diabetes in the future. Now the researchers have discovered a new receptor that brings them closer to this goal. Apparently the so-called insulin-inhibitory receptor, which the researchers called “Inceptor”, mediates insulin resistance in beta cells. These cells are responsible for producing the blood sugar hormone insulin for the entire body, but are in turn regulated by insulin themselves.
“If insulin resistance develops in the beta cells, this leads to a loss of function and leads to diabetes. Therapies that make these cells more sensitive to insulin could protect patients from the loss of beta cells or their function, ”says Ansarullah’s colleague Heiko Lickert. In experiments with mice, the researchers showed that Inceptor shields the insulin-producing beta cells from the effects of insulin. To some extent this function is important for the natural balance of blood sugar regulation. In the case of diabetes, however, Inceptor occurs in a significantly higher number – and thus possibly leads to the pathological insulin resistance of the beta cells.
Inceptor blockade as a therapeutic approach
But what happens if the function of Inceptor is genetically or medically prevented? To answer this question, the researchers first bred genetically modified mice that were completely lacking Inceptor. However, these animals died of hypoglycaemia within a few hours of their birth. In the next step, the team blocked the function of Inceptor instead with drugs using monoclonal antibodies. “The result was what we had hoped for: both the insulin signal strength and the mass of functional beta cells increased,” says Ansarullah. On the one hand, the beta cells became more sensitive to insulin and reacted to lower concentrations of the metabolic hormone. On the other hand, new beta cells were formed, which in turn produced insulin again.
“Inceptor is therefore a very promising target for treating the actual cause of diabetes, the loss and malfunction of beta cells,” says Ansarullah. Lickert adds: “A hundred years ago, Nobel Prize winner Frederick Banting emphasized in his speech on the discovery of the life-saving drug insulin that ‘insulin cannot cure diabetes, only treat the symptoms’. Nothing has changed in the last century. We now want to use the discovery of Inceptor to develop new drugs to regenerate beta cells. In this way, we could help those with type 1 and type 2 diabetes and ultimately bring about diabetes remission. “
Source: Ansarullah (Helmholtz Zentrum München) et al., Nature, doi: 10.1038 / s41586-021-03225-8