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Sugar metabolism controls intestinal regeneration

No. 49c | 14/09/2018 | by Koh

Scientists from the German Cancer Research Center and Heidelberg University have discovered a surprising connection between sugar metabolism and the adaptation of intestinal tissue to the nutritional state.

Section from the intestine of a fruit fly: Stem cells are labelled green (GFP).
© M. Boutros/DKFZ

No other tissue in our body has such a high rate of cell renewal as the intestine. Since the intestinal tissue has an enormous energy requirement, it is important for the organism to adapt the volume and structure of the intestinal tissue to changing nutrient supplies. If this regulation is disturbed, intestinal cancer can develop or the intestinal mucosa can shrink resulting in a so-called intestinal atrophy.

Intestinal stem cells are responsible for the controlled renewal of intestinal tissue. If not enough nutrients are available, the stem cells divide slowly and the intestine shrinks. A favorable nutritional situation stimulates stem cell division and the intestine recovers to its normal size. So far, however, only few results have been obtained on how this adaptation is regulated at the molecular level.

The team led by Michael Boutros from the German Cancer Research Center and the Medical Faculty Mannheim, Heidelberg University has now investigated this in cooperation with colleagues from the University of Helsinki on the intestines of the fruit fly Drosophila melanogaster. The scientists were able to show that the intestinal stem cells use a cellular pathway of sugar biosynthesis to control the rate of cell division.

A high synthesis rate of glucosamine, a glucose derivative, signals the stem cells to divide and produce cells for the new intestinal tissue. If the flies were fed a glucosamine derivative (N-acetyl-glucosamine), the intestinal stem cells proliferated independently of an otherwise poor nutritional situation. However, if the researchers genetically blocked the biosynthesis of N-acetyl-glucosamine, even a high nutrient content could not stimulate the division rate of the intestinal stem cells. Glucosamine also improved the stem cell's ability to react to insulin, a central signal molecule for the organism's nutrient status.

"The biosynthetic pathway for glucosamine was not previously known as a modulator of the stem cells in the intestine. We have discovered a surprising connection between the sugar metabolism and the adaptation of the intestine to different nutritional conditions," said Michael Boutros. If N-acetyl-D-glucosamine also plays a similar role in human intestinal cells, the current results could also gain medical importance. "Whether this actually works in humans, however, must first still be carefully examined," Boutros explains.

Jaakko Mattila, Krista Kooki, Ville Hietakangas and Michael Boutros: Stem cell intrinsic hexosamine metabolism regulates intestinal adaptation to nutrient content.
Developmental Cell 2018, DOI: 10.1016/j.devcel.2018.08.011

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.

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