Several factors have been shown to induce an increase in beta-cell mass, but exactly what triggers this in individuals consuming a high-fat diet has not been clearly established.
In a study appearing in the January issue of the Journal of Clinical Investigation, Takashi Kadowaki and colleagues from the University of Tokyo, Japan, show that in mice with high-fat diet-induced insulin resistance, changes in glucose concentration are likely to be the main trigger of increased beta-cell mass. The beta-cell mass of mice expressing only one copy of the gene encoding the sensor of blood glucose levels, GCK (Gck-/- mice), showed little increase compared with wild-type mice fed a high-fat diet, and the mice developed diabetes. One important mediator of the beta-cell mass increase downstream of GCK sensing increased blood glucose levels, and was shown to be IRS2, as expression of IRS2 in Gck-/- mice partially prevented diabetes by increasing beta-cell mass. The authors therefore suggest that novel strategies to increase beta-cell mass to treat type 2 diabetes and overcome high-fat diet-induced insulin resistance might be developed if the mechanism linking GCK and IRS2 can be determined. However, in an accompanying commentary, Gordon Weir and Susan Bonner-Weir from the Joslin Diabetes Center remind us that before we develop new therapeutics "it is essential that glucose signals involved in beta-cell replication in both health and disease be carefully defined."
By Journal of Clinical Investigation
Posted January 3rd, 2007 by harminka
