In an article published in the December 29, 2005, issue of the journal Cell, the researchers report that knocking out a single gene encoding the enzyme GnT-4a glycosyltransferase (GnT-4a ) disrupts insulin production. Importantly, the scientists showed that a high-fat diet suppresses the activity of GnT-4a and leads to type 2 diabetes due to failure of the pancreatic beta cells.

The experiments point to a mechanistic explanation for why failing pancreatic beta cells don't sense glucose properly and how that can lead to impaired insulin production, said Jamey Marth, a Howard Hughes Medical Institute investigator at the University of California, San Diego (UCSD). Marth and first author Kazuaki Ohtsubo at UCSD collaborated on the studies with researchers from the Kirin Brewery Co. Ltd., and the University of Fukui, both in Japan.

The discovery of the link between diet and insulin production offers new information that may aid in the development of treatments that target the early stages of type 2 diabetes. In its earliest phases, the disease causes failure of insulin-secreting beta cells in the pancreas, which leads to elevated blood glucose levels. As the disease progresses, the insulin-secreting beta cells overcompensate for the elevated blood glucose, and eventually pump out too much insulin. This leads to insulin resistance and full-blown type 2 diabetes.

The new studies suggest that people with an inherited predisposition to type 2 diabetes might have variations in the gene for GnT-4a, said the researchers. Worldwide, more than 200 million people have type 2 diabetes, and close to 20 million people in the United States have been diagnosed with
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
28-Dec-2005