Hyperglycaemia: imitating Claude Bernard's piqûre with drugs

Hyperglycaemia lasting for hours, has been produced in unanesthetized cats, rabbits and rats by injection into the cerebral ventricles or the cisterna magna of a variety of drugs (morphine, etorphine, pethidine, beta-endorphin, enkephalin, bombesin, TRH, cholecystokinin, naloxone, propranolol, phentolamine, chloralose, magnesium chloride and GABA). These drugs probably act at the ventral surface of the brainstem and initiate a sympathetic discharge to the adrenals which results in a prolonged release of relatively small amounts of adrenaline. When adrenaline is released in this way hyperglycaemia may be the only effect. The mechanism of the piqûre hyperglycaemia of Claude Bernard may be the same, although Bernard assumed that it resulted from an effect on the floor of the fourth ventricle, i.e. on the dorsal surface of the brainstem. However, it is clear from his description that his trochar not only pricked the floor of the fourth ventricle but penetrated to the ventral surface of the brainstem. Release of adrenaline from the adrenals is usually regarded as a stress response, as in fight, flight, fear or rage when it is suddenly released in large amounts and produces its typical cardiovascular and ocular reactions. The results now obtained with drugs injected intraventricularly or intracisternally suggest an additional physiological role for adrenaline when it is released over prolonged periods and in relatively small amounts producing only hyperglycaemia. Such a release may play a role in the day-to-day control of blood glucose, and its disturbance might underlie non-insulin-dependent diabetes.