ABSTRACT
<i>Objective</i>: The water-soluble extract of <i>Ganoderma lucidum</i> mycelia (WER) is prepared from a solid medium composed of bagasse and rice bran overgrown with <i>Ganoderma lucidum</i> mycelia. Recently, we have reported that WER had glucose-lowering effect in streptozotosin-induced diabetic mice, an animal model of type 1 diabetes. Here, we investigated whether long-term treatment with WER affects hyperglycemia and insulin resistance in KK-A<sup>y</sup> mice, a type 2 diabetic animal model with obesity.<br> <i>Methods</i>: Female KK-A<sup>y</sup> mice were given free access to water and high-fat food containing 0.5% WER for 8 weeks, with blood glucose and plasma insulin levels assessed every week. At the end of the experimental period, insulin tolerance test (ITT) was performed, and plasma levels of triglyceride, total cholesterol, HDL-cholesterol, AST, ALT and adiponectin were measured. Furthermore, expression of GLUT4 in skeletal muscle cell membrane and adipocytes was also determined by immunostaining and Western blot analysis.<br> <i>Results</i>: The mice with high-fat ingestion showed a gradual increase in levels of blood glucose and body weight. In the WER-treated mice, the blood glucose level was significantly suppressed after 2 weeks of treatment. WER also reduced plasma levels of ALT and insulin, but did not affect the other parameters. Additionally, ITT revealed that WER improved insulin sensitivity. Moreover, expression of GLUT4 in the plasma membrane of skeletal muscle cells and adipocytes of the WER-treated mice was increased.<br> <i>Conclusion</i>: These results indicate that WER has a glucose-lowering effect in type 2 diabetic mice. WER also improved hyperinsulinemia and insulin sensitivity, which may derive from enhancement of glucose uptake through GLUT4 of skeletal muscle cells and adipocytes.<br>