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In the previous paper (1), we reported that BCG cells injected into rats as Freund's complete adjuvant (FCA) enhanced insulin release stimulated by secretagogues, and insulin thus released attenuated some met abolic effects of the agonist. BCG is known as an immunopotentiator. It also has been known that BCG cell walls are as active as viable BCG in the immunotherapy of a certain guinea pig hepatoma (2, 3). Azuma et al. isolated the components, cell wall skeleton (CWS), effective in tumor therapy from BCG cell wall (4). Therefore, it seems possible that an immunosuppressant may inhibit the insulin-releasing action of FCA, and CWS may be one of the components that are responsible for stimulation of insulin secretion. In this study, we used azathioprine injection or an irradiation procedure to suppress the im munological activity of the rats, and CWS was used to clarify the latter possibility. Unless otherwise noted, male rats, 200 to 300 g, of the Donryu strain were injected i.p. with FCA (1 ml/100 g) or CWS (2.5 mg/ 100 g), and then they fasted for 24 hr and used for experiments. The insulin concen tration in plasma was determined by the radioimmunochemical method (5). Isopro terenol (200 ,ag/100 g) was also used as a secretagogue in this study (1). Eight hundred rad X-ray irradiation of rats was carried out with the Toshiba Model KXC-18-2 instru ment using a 0.5 mm Cu filter at 180 KV, 25 mA. In the first experiment, rats were injected i.p. with azathioprine dissolved in saline containing 0.1% methyl cellulose at a dose of 40 mg/kg/day for 4 days before the experi ment. FCA was injected 24 hr after the last injection of the inhibitor. Twenty-four hr after the injection of FCA, the stimulatory action of isoproterenol on the plasma level of insulin was tested. However, the immuno suppressant did not inhibit the supersensitiz ing action of FCA on insulin secretion stimulated by isoproterenol (data not shown). FCA also enhanced insulin release stimulated by isoproterenol even in the irradiated rats as effectively as in the control rats (Fig. 1). These two experiments suggest that the stimulatory action of FCA on insulin secretion stimulated by isoproterenol was not mediated by its immunopotentiating action. However, we cannot rule out any effects due to the activation of the immunological system by FCA on insulin secretion since irradiation itself enhanced insulin release stimulated by isoproterenol as shown …

Potentiation of insulin secretory response of rats by cell wall skeleton extracted from BCG cell wall.