Description:Dietary fructose, especially in the context of a high-fat western diet, has been linked to type 2 diabetes. Although the effect of fructose on liver metabolism has been extensively studied, a significant portion of the fructose is first metabolized in the small intestine. Here we report that dietary fat enhances intestinal fructose metabolism, which releases glycerate into the blood. High systemic glycerate levels reduce pancreatic islet sizes and ß-cell content, thus inducing glucose intolerance. Our findings provide an additional link between dietary fructose and diabetes that is modulated by dietary fat.