Insulin resistance is a condition in which insulin, which is a hormone that lowers blood glucose, becomes less sensitive and less effective, and is considered to be one of the important causes of diabetes and metabolic syndrome.Now, a research group at Juntendo University has discovered that insulin resistance develops in skeletal muscle after only 24 hours of inactivity.
Insulin resistance is thought to appear primarily with obesity, but even in the absence of obesity, insulin resistance may develop due to inactivity such as increased stay home or sitting time.Therefore, in this study, we first created an inactivity model in which one leg of a mouse was cast-fixed, and investigated its effect on metabolic function.
The results showed that insulin sensitivity of skeletal muscle was halved and insulin resistance occurred even with inactivity for only 24 hours.Insulin resistance was further exacerbated by combining inactivity with a high-fat diet.
Since it is thought that the accumulation of a lipid called diacylglycerol (DG) in skeletal muscle cells inhibits insulin signal transduction and reduces insulin sensitivity, the amount of DG in skeletal muscle was also analyzed.Then, it was found that the amount of DG doubled due to inactivity and further increased in combination with a high-fat diet, and insulin resistance occurred with the increase.
It was revealed that Lipin1, a lipid-metabolizing enzyme that produces DG, is involved in this. Inactivated Lipin1 inactivated skeletal muscle did not develop DG accumulation or insulin resistance due to inactivity.On the other hand, in the human experiment, the Lipin24 expression level and the skeletal muscle DG level were significantly increased by the inactivity caused by immobilizing one leg in a cast for 1 hours, and the results consistent with the mouse experiment were obtained.
From the above, the mechanism by which DG accumulation occurs in skeletal muscle due to activation of Lipin24 even with a short inactivity of 1 hours and insulin resistance occurs has been clarified.This result may lead to the development of new lifestyle-related disease preventive measures targeting Lipin1.
Paper information: [American Journal of Physiology Endocrinology and Metabolism] Short-term physical inactivity induces diacylglycerol accumulation and insulin resistance in muscle via lipin1 activation Causes insulin resistance)
