The effect of insulin upon pyruvate utilization by pigeon muscle.

The recent demonstration by Cori (1) that the hexokinase reaction is controlled by the interaction of insulin, anterior pituitary, and adrenal cortical hormones naturally raises the question as to whether the chemical action of insulin can be totally explained on the basis of this’one effect. The evidence indicating that insulin is concerned more directly with oxidative reactions in the carbohydrate cycle is somewhat equivocal. However, there are experiments in the literature showing that insulin is concerned in oxidative reactions, particularly of pyruvate, which cannot be ignored. For example, Krebs and Eggleston (2) showed that the oxygen uptake of pigeon breast muscle mince was prolonged and therefore increased by insulin. This observation was amply confirmed by others (3-5). The observation of Stadie and Zapp (6) that pigeon breast muscle mince as customarily prepared contains no glucose and little or no glycogen and is dependent almost exclusively upon hexose phosphate for its metabolism would appear to exclude any possible r&e of hexokinase in experiments in vitro. In other words, this observation of Krebs and Eggleston shows that insulin may act on some enzyme system other than hexokinase. The inability to demonstrate an insulin action with muscle minces from other species (3-5) has made it difficult to assess the significance of this finding in relation to the general problem of insulin action. Futher evidence must also be considered. Banga, Ochoa, and Peters (7) reported that insulin increases the utilization of pyruvate by minces of pigeon brain. Delrue and De Keyser (8) found that rabbits injected with pyruvate showed significantly lower blood pyruvate levels if simultaneously treated with insulin. However, the experiments of Bueding, Fazekas, Herrlich, and Himwich (9), showing that pyruvate blood levels in diabetic animals following the injection of glucose were low but could be significantly elevated by antecedent injection of insulin, have tended to support the concept that pyruvate formation rather than utilization was impaired in the diabetic state. But the evidence at hand does not warrant the con-