The addition of 10-"M insulin to a cell-free system from rat liver promotes the release of messengerlike RNA from isolated prelabeled nuclei. The stimulation was similar whether the nuclei were preincubated with insulin, or if insulin was added directly to the cell-free system with or without a protease inhibitor. Dot blot hybridization using cloned cDNA for a2,-globulin mRNA showed that this was one of the messages whose release was enhanced by insulin. Nuclei isolated from rats treated with either of the antidiabetics tolbutamide or tolazamide showed no increase in RNA release in the presence of insulin over the concentration range 10-5-10-14 M . Furthermore, these nuclei did not release detectable levels of aZuglobulin mRNA.Key words: insulin, anti-diabetic drugs, tolazamide, tolbutamide, RNA transport, olz,-globulin mRNAInsulin is known to produce both immediate and late metabolic effects. The latter may be associated with the internalization of the hormone and its binding to high-affinity sites on the nuclear membrane [1,2]. Insulin binding to the nuclear membrane has been shown to stimulate the nuclear pore ATPase [3] and mRNA, but not rRNA, efflux from the nucleus to the cytoplasm in a cell-free system [4]. Since these latter experiments required insulin concentrations greater than physiological, it was of interest to determine the cause of the high insulin requirement and, if possible, to modify the system to respond to lower insulin levels.Among the specific long-term effects of insulin is the enhancement of the concentration of mRNA for albumin [5], az,-globulin [6], and tyrosine amino transferase [ 7 ] . If nuclei incubated in the cell-free system, which has previously been shown to release functional mRNA [8], are responding to insulin as do nuclei in vivo, it should be possible to detect an increased amount of these mRNAs in the RNAs released in vitro in the presence of insulin. The availability of a cloned cDNA to a2"-globulin mRNA [9] makes such a study feasible at this time.One of the acute in vivo effects of the oral antidiabetic drugs tolbutamide and tolazamide is to increase the levels of circulating insulin. These drugs have been