Biphasic effect of pertussis vaccine on serum insulin in mice

Administration of pertussis vaccine, consisting of whole, killed Bordetella pertussis organisms, causes hyperinsulinemia and enhanced secretion of insulin in response to a variety of secretagogues in rats and mice. In examining the time course and properties of this phenomenon, we discovered two distinct and separate effects of the bacteria on glucose and insulin levels in mice. First, a heat-stable (80 degrees C for 30 min) component causes a brief hyperinsulinemia which is +measureable by 1 h, maximal at 8 h, and ends in less than 48 h. This effect appears to be due to B. pertussis endotoxin, is mimicked by Escherichia coli endotoxin, and is associated with a transient, mild hypoglycemia. Second, there is a heat-labile component of the B. pertussis organism which induces a sustained (greater than 14 days), dose-dependent hyperinsulinemia which reaches a maximum at 5 to 7 days and has no associated hypoglycemia. The two effects are further distinguishable in that the early, endotoxin-induced hyperinsulinemia exhibits the normal suppressibility by exogenous epinephrine, whereas epinephrine markedly enhances the hyperinsulinemia occurring at 7 days. These two effects of B. pertussis appear to be mediated by different mechanisms and may be important in the well-recognized reactogenicity of pertussis vaccine in humans.