Recent studies provide molecular clues to the details of how a high-fat diet contributes to the development of type 2 diabetes and point the way toward a possible means of countering the disease (Ohtsubo K et al. Nat Med. 2011;17:1067-1075).
Investigators at the Center for Nanomedicine, a collaboration between the University of California, Santa Barbara, and Sanford-Burnham Medical Research Institute, found that the pancreatic beta cells of mice fed a high-fat diet had reduced expression of 2 transcription factors, FOXA2 and HNF1A. This in turn diminished expression of GnT-4a glycosyltransferase, an enzyme required for the transport of glucose across pancreatic beta-cell membranes. Affected mice exhibited signs typical of metabolic syndrome, including hyperglycemia, impaired glucose tolerance, and hyperinsulinemia. Preserving GnT-4a function in mice blocked the onset of diabetes, even in obese animals.