Intermittent Leucine Deficiency Regulating Insulin Sensitivity
Abstract
The pathological feature of type 2 diabetes is insulin resistance, which, if not controlled in time, will cause a variety of serious complications, including atherosclerosis, neuropathy, retinopathy and so on. Our research team found that after treated with the seven cycles of intermittent leucine ldeprivation (1 cycle=1 day leucine deprivation+ 3 days of control diet), even return to normal diet, the enhanced insulin sensitivity on the wild type mice formed through metaboliic memory remained nearly 3 months at least. Further studies showed that the function of intermittent leucine deprivation depends on the increase of hepatic GCN2 expression. The expression of GCN2 is relied on the up-regulation of the demethylase Gadd45b to function on the CpG sites of its promoter and then affect the methylation level of GCN2.
In conclusion, this work provides important evidence that the liver can also form metabolic memory and the regulation of amino acid deficient sensor GCN2 at the epigenetic level. It provides an important theoretical basis for understanding the pathogenesis and treatment of diabetes, and also provides a new idea for nutrition intervention of diabetes. This work was published in Diabetes in 2021.
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