MANF regenerates insulin-producing β-cells

One of the main goals of improving current diabetes therapy is to find ways to protect β-cells from stress and activate their regeneration, said the report of a study conducted by the University of Helsinki.

The research team led by Maria Lindahl have found that the removal of mesencephalic astrocyte–derived neurotrophic factor (MANF), specifically from β-cells, in adult mice results in loss of β-cells in diabetes, said a press release issued by the university on Wednesday.

“This indicates that MANF expression is needed for the survival, maintenance and function of pancreatic β-cells in mice. MANF was also found to protect stressed β-cells from death and to induce the proliferation of β-cells from old mice,” said Lindahl.

“This discovery further suggests that MANF has therapeutic potential for the treatment of Type 1 and Type 2 diabetes, where β-cell protecting and regenerating therapies are not available,” said Tatiana Danilova, a member of the research team.

In previous collaboration studies directed by Professor Mart Saarma and Professor Timo Otonkoski at the University of Helsinki, MANF deficiency in mice was found to lead to diabetes due to the progressive loss of insulin-producing pancreatic β-cells. MANF was found important for the survival and proliferation of both human and mouse β-cells in culture.

Diabetes mellitus is characterised by high blood glucose levels. These high levels are caused by the inability of the insulin-producing β-cells in the pancreas to maintain sufficient levels of circulating insulin.

Current medications alleviate diabetic symptoms, but they cannot reconstitute physiological insulin secretion. This increases the risk of vascular complications, which might lead to conditions such as heart disease, stroke and kidney disease.

Typical for Type 1 and the later stages of Type 2 diabetes is β-cell loss preceded by sustained cell stress. The stress is caused by problems in dealing with aggregated proteins that lead to the self-destruction of β-cells.