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Menin Gene Mutation made Insulin Secreting Cells to Proliferate

Acute loss of a protein named menin – involved in tumor-suppression or cell-proliferation-suppressing function resulted in the proliferation of pancreatic islet cells, which again affected blood sugar// regulation - researchers at the University of Pennsylvania School of Medicine reports.

In humans menin gene (Men1) mutation can lead to a genetic disease called Multiple Endocrine Neoplasia type 1 (MEN1) and this discovery also has implications for diabetes treatment.

MEN1 patients develop mostly benign tumors or hyperplasia (over proliferation of cells) in several endocrine organs, such as parathyroids and pancreatic islet cells. Normally, the menin protein has a tumor-suppressing or cell-proliferation-suppressing function. Loss of menin can cause proliferation of pancreatic islet cells, but not the adjacent exocrine cells that secrete proteins other than insulin.

The researchers developed an animal model that allowed for precise timing in ‘cutting’ the Men1 gene from the genome of knock-out mice. They showed that within seven days of excising Men1, pancreatic islet cells proliferated in the mice. Previously, other labs could only see proliferating islet cells after months of Men1 excision because they could not precisely time the process. ‘Our results show an acute effect of Men1 excision and directly link Men1 to repression of pancreatic islet cell proliferation,’ says senior author Xianxin Hua, MD, PhD, Assistant Professor of Cancer Biology at Penn's Abramson Family Cancer Research Institute.

The researchers excised Men1, the gene encoding the protein menin, from both islet cells and adjacent exocrine cells in the pancreas, but only in islet cells did they observe cells proliferating. This is important because Men1 mutations largely cause endocrine hyperplasia or tumors, but not exocrine tumors. ‘Our results showing preferential effects on islet-cell proliferation could at least in part explain that the loss of menin only l
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