Study reveals possible genetic link to inherited form of Diabetes – University of Copenhagen

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05 March 2015

Study reveals possible genetic link to inherited form of Diabetes


In a recent study scientists at the University of Copenhagen revealed that a gene whose mutation can lead to kidney dysplasia in humans may also cause diabetes. In mice, its mutation results in the formation of renal and pancreatic cysts, as well as a reduction in beta cells, which may later in life lead to diabetes.

PhD student Laurence Lemaire and a team of researchers led by Professor Anne Grapin-Botton from the Danish Stem Cell Center (Danstem) at the University of Copenhagen and scientists at the Swiss Federal Institute of Technology (EPFL) found that mice lacking the Bicc1 gene develop cysts in the kidney and pancreas. In addition they make less insulin-producing beta cells. The results have just been published in the scientific journal Development and may eventually lead to better prenatal counseling and screening for diabetes in patients with kidney dysplasia.

Why does a mutation of one gene affect several organs?

To make an organism during embryonic development, many genes are used for more than one purpose. Bicc1 is such a gene and it is expressed in the tubes of the pancreas and those of the kidney. This is the reason why its mutation affects both organs. In both organs, the absence of Bicc1 ultimately causes enlargement of the tubes. These enlargements, called cysts, usually result in organ dysfunction. In the pancreas specifically they are lined by cells which in case of cyst formation convert less efficiently into beta cells.

When the formation of the pancreas is impaired, people may develop diabetes later in life

"If less pancreatic beta cells are formed in an embryo, there is an increased risk of diabetes later in life

“The beta cells are the cells that produce insulin, the hormone that regulates the level of sugar in our blood. We as humans, and mice as well, form more beta cells than we need during embryonic development, but if we have less cells to begin with, any other problem that happens to these cells later in                                                                life is amplified” says Prof. Grapin-Botton

What can we learn from this recent discovery?

Although the Copenhagen team, together with geneticists in Paris, has previously found that patients with mutations in the Bicc1 gene develop kidney dysplasia, it remains to be seen if some of the patients later develop diabetes, as suggested by the mouse experiments. The kidney cysts and diabetes syndrome is a heritable disease and affected patients often have HNF1B mutations (a syndrome named MODY5). But for many patients we do not know the causal gene for their disease. BICC1 may be one possible gene to act in the same signalling pathway as HNF1B and to cause similar syndromes. In affected patients, the kidney disease is the most severe and will always be detected first, but knowing the gene involved can lead physicians to watch out for diabetes.

Figure: Slices of the pancreas: enlarged ducts (orange)  in the absence of Bicc1 (large hole in bottom panel) and decrease of beta cells (light blue) as compared to a normal pancreas (top panel). The dark blue marks every cell of the organ.

You can find more information about this research on the Grapin-Botton Laboratory website.

The work was published:

Lemaire, Laurence A., Joan Goulley, Yung Hae Kim, Solenne Carat, Patrick Jacquemin, Jacques Rougemont, Daniel B. Constam & Anne Grapin-Botton (2015). Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis. Development, 142(5), 858-870, doi: 10.1242/dev.114611.