Fig 2. Model for PTX- and ACT-induced hyperinsulinemia.

Following infection, B. pertussis produces PTX, which acts not only within the respiratory tract but also directly on insulin-secreting pancreatic beta cells. Within these cells, PTX inhibits Gα_i/o signaling that ordinarily inhibits adenylate cyclase, the enzyme responsible for cAMP synthesis. This leads to increases in cAMP and activates PKA, a key stimulator of insulin release. In parallel, B. pertussis also secretes ACT, which directly increases cAMP levels to also produce hyperinsulinemia and subsequent hypoglycemia in the host. ACT, adenylate cyclase toxin; PKA, protein kinase A; PTX, pertussis toxin.