Glycogen synthase kinetics in isolated human adipocytes: an in vitro model for the effects of insulin on glycogen synthase.

Glycogen synthase which catalyzes the incorporation of uridine dipophosphate glucose into glycogen is found in muscle, liver, and fat. The activity of this enzyme is increased by insulin through a dephosphorylation mechanism. Because of the critical role of glycogen synthase in glucose storage and overall glucose metabolism, it is important to assess the status of the activity of this enzyme in normal humans as well as in individuals with pathological conditions, such as non-insulin-dependent diabetes mellitus. However, in human subjects, studies of the regulation of glycogen synthase in vivo are time consuming and tedious. The present study was, therefore, undertaken to establish whether adipocytes isolated from subcutaneous adipose tissue biopsies from normal human subjects could be used to assess the effect of insulin in vitro on glycogen synthase activity. Regulation of glycogen synthase in human adipocytes by glucose 6-phosphate and uridine disphosphate glucose was found to be somewhat different than that reported for the regulation of this enzyme in tissues from other species. The adipocyte was found to be a sensitive model for insulin activation of this enzyme. Glycogen synthase was stimulated twofold by an insulin concentration of as low as 1 ng/ml, while half-maximal activation of enzyme activity occurred at 0.4 +/- 0.1 ng insulin/ml. The present studies indicate that the isolated human subcutaneous adipocyte may serve as a useful model for in vitro investigation of the effects of insulin on glycogen synthase.