It is proposed that insulin has a cardinal role in the regulation of serum potassium levels in man, which may be of greater importance than the effect of insulin on glucose metabolism. Although the first described action of insulin was on glucose transport, it is a hormone with many functions some of which may operate in a metabolic hierarchy depending on the relative importance of the action required. Insulin also promotes the transport of potassium ions from the extracellular space to the intracellular space and it is suggested that there are occasions where this action may take place at the expense of glucose regulation. In metabolic terms, tight control of serum potassium is of greater importance than precise control of serum glucose, because quite small variations in serum potassium may cause death whereas wide variations in serum glucose may be tolerated. Serum potassium levels generally remain very stable despite large daily variations in potassium intake. It follows that potassium control mechanisms must be of outstanding efficiency as serious disturbances of potassium balance are relatively uncommon. 'Nature makes experiments on Man': shadowy but important physiological mechanisms that may almost be taken for granted in normal health are often brightly illuminated by unusual pathological conditions. This paper describes two remarkable patients who presented with extreme hyperkalaemia. This condition was the result of simultaneous insulin and aldosterone deficiency occurring because of concomitant diabetes and Addison's disease. Other medical conditions with disturbances in aldosterone, insulin and potassium control will be referred to in support of the hypothesis that insulin secretion is central to potassium regulation. This hypothesis explains the secondary disturbances in glucose metabolism that occurs in clinical situations where the primary problem is perturbation of potassium regulation.
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