Researchers identify potential target for treatment among patients with type 2 diabetes

Aug. 5, 2022
Discovery could prevent insulin resistance.

In a potential game changer for patients with type 2 diabetes, a team of researchers at the Diabetes, Obesity, and Metabolism Institute (DOMI) at the Icahn School of Medicine at Mount Sinai has identified a therapeutic target for the preservation and regeneration of beta cells (β cells)—cells in the pancreas that produce and distribute insulin.

The discovery could prevent insulin resistance and thus have significant benefits for millions of people worldwide. The results of the study were published in Nature Communications in July.

All major forms of diabetes are caused by insufficient β-cell mass. When blood glucose levels rise in the body, such as in response to a high-fat diet, β cells respond by producing and releasing more insulin to bring blood glucose levels under control. But prolonged high blood glucose, known as hyperglycemia, can impair the ability of β cells to produce and secrete insulin. This results in a vicious cycle of ever-increasing glucose levels and ever-declining β-cell function, leading to β-cell death — a phenomenon known as glucose toxicity. Thus, preservation and regeneration of β cells is a therapeutic goal for diabetes.

The Mount Sinai research team found a molecular mechanism that appears to be involved in β-cell preservation and regeneration involving carbohydrate response-element binding protein (ChREBP). The researchers showed that production of a hyperactive isoform of this protein, ChREBPβ, is necessary to produce more β cells in response to an increased demand for insulin in the body due to a high-fat diet or significant glucose exposure. However, prolonged, increased glucose metabolism can result in a vicious cycle in which ChREBPβ is overproduced, resulting in glucose toxicity in the β-cells and their subsequent death.

The research team found that it was possible to counteract the effects of ChREBPβ and the β-cell death they observed by increasing expression of an alternate form of the protein, ChREBP⍺, or by activating nuclear factor-erythroid factor 2 (Nrf2)—a protein that protects cells from oxidative damage—in mice and human β cells, thus preserving β-cell mass.

Mount Sinai release