Evidence for a role of endogenous insulin and glucagon in the regulation of potassium homeostasis

Studies were designed to determine if increased serum K⁺ stimulates insulin and/or glucagon secretion in vivo, and if so, their possible roles in K⁺ homeostasis. KCl (4 mEq. per kilogram per hour) was infused intravenously for 60 minutes in 12 conscious dogs. Within 20 minutes, as serum K⁺ reached 5.9 mEq. per liter (S.E.M. ± 0.2), both hormones increased in all dogs; at 60 minutes K⁺ reached 7.7 mEq. per liter (S.E.M. ± 0.2), insulin had risen 30 μU per milliliter (S.E.M. ± 7), glucagon 80 pg. per milliliter (S.E.M. ± 14), and glucose 7 mg. per 100 ml. (S.E.M. ± 2). Serum K⁺ increment (Kl) averaged 0.05 mEq. per liter per milliequivalent infused (S.E.M. ± 0.005) and postinfusion K⁺ disappearance (KD) averaged 2.5 mEq. per liter per hour (S.E.M. ± 0.2). The role of each hormone was individually examined by preventing secretion of the other. To prevent kaliogenic insulin secretion, 11 dogs were alloxanized and controlled with insulin before the study. In these dogs KCl dose had to be reduced to < 3.3 mEq. per kilogram per hour to avoid electrocardiograph (ECG) changes, but other evidence of potassium intolerance appeared; KI rose to 0.075 (S.E.M. ± 0.008) and KD fell to 1.63 (S.E.M. ± 0.2) (p < 0.02; < 0.05). Glucagon rose 300 pg. per milliliter (S.E.M. ± 76) and, with hyperinsulinemia effectively prevented, glucose rose 59 mg. per 100 ml. (S.E.M. ± 18). When, however, insulin was administered with the KCl, potassium intolerance was corrected; KI in these dogs was only 0.035 mEq. per liter per milliequivalent of K⁺ infused. To assess the role of glucagon, kaliogenic glucagon secretion was prevented by inducing hyperglycemia averaging 150 mg. per 100 ml. by glucose infusion (15 mg. per kilogram per minute), before and throughout the KCl infusion. Now KCl increased insulin 19 μU per milliliter (S.E.M. ± 7) and, with hyperglucagonemia prevented, glucose declined 41 mg. per 100 ml. (S.E.M. ± 6) in 60 minutes; KI and KD were unchanged. It is concluded that K⁺ stimulates insulin and glucagon. Without glucagon, kaliogenic hyperinsulinemia causes hypoglycemia but K⁺ is handled normally. Without insulin, however, K⁺ tolerance and disappearance fall markedly and exaggerated kaliogenic hyperglucagonemia causes hyperglycemia. This suggests that normally hyperkalemia elicits its own "self-treatment" with endogenous glucose and insulin, insulin increasing K⁺ tolerance and glucagon providing enough glucose to prevent hypoglycemia.