Dogs with ligated ureters were infused with KCI at rates that varied from 0.2 to 3 mEq/kg/hr, and infusion continued until the onset of cardiac manifestations of hyperkalemia, when serum potassium ranged between 9.9 and 11.0 mEq/L. It was found that ligated dogs were able to remove much of the infused potassium from extracellular fluid despite the suppression of urinary excretion. Pancreatectomized dogs lost the ability to remove infused potassium from extracellular fluid; treatment with insulin restored it completely. Addition of insulin (SU/kg/hr) to the infused KCI markedlyaugmented both tlte rate of potassium removal from extraceUular fluid and the arnount sequestered outside the extracellular compartment. In non-pancreatectomized liga ted dogs, the maximal rate of potassium removal without exogenous insulin was ~ 0.5 mEq/kg/hr, and maximal potassium sequestered 3.3 mEq/kg. Insulin added to the KCI infusion increased the rate to ~ 1.6 mEq/kg/hr and the arnount sequestered to -6.2 mEq/kg. Insulin may have an important physiological role in the regulation of serum potassium.

The disposal of intravenous glucose (%/min ± SE) was markedIy delayed in rats anesthetized with 50 mg/kg of intraperitoneal sodium pentobarbital (K=2.14 ± 0.23) compared to conscious litter mates (K=3.95 ± 0.21). There were no differences in fasting plasma glucose concentrations or in the insulin response to administered glucose. Diaphragms and epididymal fat pads removed from anesthetized animals differed in their vitro response to glucose and insulin only by a small (10%), but significant (p <0.05), decrease in the basal glucose uptake of the muscle tissue. Sodium pentobarbital (0.1 mg/mi) added in vitro inexplicably stimulated insu1in-mediated glucose uptakc of hemidiaphragms from untreated rats but had no effect on adipose tissue metabolism. The pathogenesis of pentocarbital-induccd glucose intolerance in the rat remains to be elucidated Horm. Metab. Res. 3: 243-247 (1971) K e y -Wo r d s: Pentobarbital -Glucose Intolerance -Barbiturates -Carbohydrate Metabolism -Insulin Response

No abstract

To gain insight into the mechanism of the altered carbohydrate metabolism in thyrotoxicosis, intravenous glucose tolerance tests (IVGTT) and pancreatic suppression tests (PST) were performed in hyperthyroid rats (0.1 mg/kg T4 X 5 days) to assess insulin secretion and action in vivo. Thyroid hormone injections significantly increased T4 levels (182.8 nM +/- 11.6 (SEM) versus 50.2 +/- 6.4; P less than 0.001) and baseline glucose concentrations (9.3 mM +/- 0.2 versus 7.1 +/- 0.2; P less than 0.001). Body weights, basal insulin concentrations, glucose concentrations during IVGTT, glucose disappearance rates and steady state plasma glucose levels (SSPG) were normal. Insulin concentrations during the glucose tolerance test and during the PST were significantly decreased. The metabolic clearance rate of insulin (ml/min/kg +/- SEM) was significantly (P less than 0.01) increased (54.4 +/- 3.5 versus 41.6 +/- 2.3) in the hyperthyroid rats. If the different baseline glucose values were subtracted from the glucose concentrations achieved during the 2 tests, both the glucose disappearance rate and the fall in SSPG levels were significantly enhanced in the T4-injected animals. Thus, in the hyperthyroid rat, insulin secretion is decreased, the clearance of insulin is increased and insulin sensitivity is either normal or possibly enhanced.

In a dog K loaded by infusion of 2 mEq KCl/kg/hr, kaluresis plays a relatively small part in slowing the development of hyperkalemia and cardiotoxicity. These are largely retarded by a non-renal mechanism that transfer most of the infused K from extracellular to intracellular fluid. Treatment with beta receptor blocking dosages of propranolol significantly reduces K transfer capacity, but it also markedly diminishes the KCl stimulated secretory response of insulin, a powerful mediator of K transfer. In dogs in which diminution of the insulin response is prevented by administration of exogenous hormone, beta receptor blockade has no effect on K transfer capacity. Thus, it appears that decreased insulin secretion is responsible for the observed fall of K transfer capacity in dogs with beta receptor blockade. However, other evidence suggests that our results can also mean that a K load elicits the secretion of enough insulin to mediate K transfer in the presence of beta receptor blockade; if the hormone response is absent or deficient, beta receptors may be importantly involved in mediation of K transfer to intracellular fluid.