Missing Sugar Molecule Raises Diabetes Risk in Humans

A new study claims that an evolutionary gene mutation that occurred millions of years ago caused the human inability to produce a specific kind of sugar molecule that appears to make people more vulnerable to developing type 2 diabetes.

Sialic acids are sugar molecules found on the surfaces of all animal cells, where they act as vital contact points for interaction with other cells and with their surrounding environment. Virtually all mammals produce two types: N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Humans, however, are an exception; a mutation in a gene called cytidine monophosphate–sialic acid hydroxylase (CMAH) occurred 2 to 3 million years ago, inactivating an enzyme in humans that catalyzes production of Neu5Gc by adding a single oxygen atom to Neu5Ac.

Researchers at the University of California, San Diego (UCSD; USA) and the Children's Hospital (San Diego, CA, USA) compared two groups of mice; one with a functional CMAH gene, the other with an altered CMAH gene similar to the human mutation. Both groups of mice were fed a high-fat diet. Mice in both groups became obese and developed insulin resistance. However, only mice with the CMAH gene mutation experienced pancreatic beta cell failure--the cells that make and release insulin.

According to the researchers, the findings help refine understanding of why obese humans appear to be particularly vulnerable to type 2 diabetes, and also suggest that current animal models used to study diabetes may not accurately mirror the human condition. In clinical terms, further research to determine how sialic acid composition affects pancreatic beta cell function may reveal new strategies to preserve the cells, improve insulin production, and prevent diabetes. The study was published early online on February 24, 2011, in the journal of the Federation of American Societies of Experimental Biology (FASEB).

"It opens up a new perspective in understanding the causes of diabetes. Given the global epidemic of obesity and diabetes, we think that these findings suggest that evolutionary changes may have influenced our metabolism and perhaps increased our risk of the disease,” concluded corresponding study author, Jane Kim, MD, an assistant professor in the UCSD department of pediatrics.

Related Links:
University of California, San Diego
Children's Hospital San Diego