NEW YORK (Reuters Health) – A team at the University of California at San Diego has identified a gene that encodes an enzyme that enables pancreatic beta cells to recognize glucose and secrete insulin.
In a study published in the December 29th issue of Cell, Dr. Jamey D. Marth and colleagues describe the gene that encodes GnT-4a glycosyltransferase (GnT-4a).
Without the glucose transporter enzyme GnT-4a, beta cells fail to produce insulin when exposed to glucose and fat, resulting in type 2 diabetes.
Furthermore, a high fat diet suppresses the GnT-4a enzyme, Dr. Marth says.
The investigators found that “the GnT-4a enzyme is essential for the production of a complex-type glycan ligand on the pancreatic beta cell Glut-2 (glucose transporter 2) glycoprotein that stabilizes Glut-2 cell surface expression by a lecithin-receptor binding mechanism.”
Dr. Marth and colleagues studied mice that did not carry the GnT-4a gene and found that the animals initially had high blood glucose levels, which progressed to beta cell failure followed by the development of type 2 diabetes. Normal mice that carried the GnT-4a enzyme who were fed a high-fat diet had reduced GnT-4a expression, followed by the chain of events leading to type 2 diabetes.
“Our findings suggest that the current human epidemic in type 2 diabetes may be a result of GnT-4a enzyme deficiency,” Dr. Marth commented in a university release.
If further research confirms the UCSD team’s findings, one possible clinical application would be the development of therapeutic agents that boost GnT-4a levels.
Dr. Marth is currently working on this.
GnT-4a inhibitors may also be useful in preventing a number of diseases inked to hyperinsulinemia, such as cancer and cardiovascular disease.
Fonte: Fonte : Cell 2005;123:1307-1321