Diabetes: Unconventional neurotrophic factor MANF may regenerate insulin-producing cells in the pancreas

MANF has therapeutic potential for the treatment of Type 1 and Type 2 diabetes.

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.

One of the main goals in improving current diabetes therapy is to find ways to protect β-cells from stress and activate their regeneration.

Maria Lindahl and her team at the University of Helsinki have found that the removal of mesencephalic astrocyte–derived neurotrophic factor MANF specifically from β-cells in adult mice results in the loss of β-cells in diabetes.

"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," Maria Lindahl says.

“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,” says Tatiana Danilova from Maria Lindahl's team.

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


Original publication:

Danilova T, Belevich I, Li H, Palm E, Jokitalo E, Otonkoski T, Lindahl M. MANF is required for the postnatal expansion and maintenance of the pancreatic β-cell mass in mice.  Diabetes. 2018 Oct 10. pii: db171149. doi: 10.2337/db17-1149