Transgenic Mice With Increased Hexosamine Flux Specifically Targeted to β-Cells Exhibit Hyperinsulinemia and Peripheral InsulinResistance

摘要

Hexosamines have been shown to mediate effects of hyperglycemia and so-called "glucose toxicity" in insulin-sensitive tissues. To determine the effects of hexosamines on insulin synthesis and secretion, trans- genic mice were created to overexpress the rate-limit- ing enzyme for hexosamine synthesis, glutamine:fruc- tose-6-phosphate amidotransferase (GFA), specifically in β-cells. GFA activity in islets of heterozygous trans- genic mice was elevated 76/100 compared with littermate controls.