Metabolic effects of Bordetella pertussis
The present work confirmed that B. pertussis infection or pertussis toxin produce hypoglycaemia in mice. The hypoglycaemia was associated with hyperinsulinaemia, and both were abolished by destruction of the pancreatic β cells with alloxan. Impaired glucose counterregulatory mechanisms may also contribute to pertussis-induced hypoglycaemia, as the hypoglycaemic action of insulin was prolonged in pertussis infected mice. On the other hand, impaired responsiveness to lower doses of insulin was found. Pertussis-induced hyperinsulinaemia had two components. First, the increase in serum insulin in response to food intake was both greater and more prolonged in pertussis-infected mice. Second, infected or pertussis toxin-treated animals, unlike controls, showed a marked increase in serum insulin in response to certain stresses, such as ether, histamine, anoxia and 2-deoxyglucose. However, other stresses (LPS, cold and hypoxia) did not cause hyperinsulinaemia in pertussis infected mice. Stress-induced hyperinsulinaemia was also seen in normal mice receiving the a2- adrenoceptor blocking drug idazoxan. Stress-induced hyperinsulinaemia in a2 adrenoceptor blocked mice, but not in pertussis-treated mice, was prevented by β adrenoceptor blockade using propranolol. Adrenal demedullation or ganglionic blockade (using hexamethonium) in normal mice also allowed stress induced hyperinsulinaemia. Thus, adrenal medullary catecholamines may normally serve to prevent stress induced hyperinsulinaemia, which becomes unmasked when they are absent or when their action is prevented. Stress-induced hyperinsulinaemia in pertussis treated mice was unlikely to involve autonomic, cholinergic oropioid mechanisms as it was not blocked by hexamethonium, atropine or naloxone. Human infants with pertussis showed no hypoglycaemia compared with non-pertussis controls, although their plasma insulin concentrations were slightly but significantly raised. It remains possible that hyperinsulinaemia with resultant profound hypoglycaemia might occur in susceptible patients following exposure to pertussis-toxin (either during the disease or following vaccination).