Phytochemicals, Their Intestinal Metabolites, and Skeletal Muscle Function

Abstract Skeletal muscles are the largest tissue in our body and play an important role in maintaining glucose homeostasis. After contriving a simple and rapid glucose uptake assay system by adopting cultured L6 myotubes, phytochemicals that promote glucose uptake under the condition of insulin absence were screened. All the screened phytochemicals [(resveratrol, piceatannol, aspalathin, nepodin, gingerol, genistein, daidzein, equol, enterolactone (ENL)] activated 5′-adenosine monophosphate-activated protein kinase (AMPK) and hence promoted translocation of glucose transporter 4 to plasma membrane. These phytochemicals suppressed the rises in blood glucose levels and improved the glucose intolerance in type 2 diabetes (T2D) model mice (db/db, ob/ob, KK-A y ). Daidzein and nepodin also activated AMPK in gastrocnemius muscle of db/db mice. Genistein and daidzein reduced urinary glucose excretion in KK-A y mice. Some microbial metabolites in the intestine such as equol from daidzein and ENL from lignans promoted glucose uptake in vitro, suppressed the rises in blood glucose levels, and improved glucose intolerance in vivo at low doses. Phytochemicals that have potential to stimulate glucose uptake in muscle cells are suggested to be antidiabetic. Thus, studies on novel compounds that activate skeletal muscle glucose uptake and AMPK would be useful for the development of new treatment of insulin resistance and T2D.