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Insulin Recoverable from Tissues

In this report we describe the insulin concentrations in plasma and in brain, kidney, liver, heart, and other tissues of rabbits and dogs as well as of rats and mice of different strains. In the larger animals, insulin concentrations in the brain never exceeded plasma levels. In rats, brain concentration averaged no more than twice plasma levels, compared with the 25-fold tissue:plasma ratio reported by others. Since there is no reason to believe that the biosynthetic mechanisms are different in the brains of large and small mammals, Our results suggest that the insulin found in the brain is due in part to that in vascular spaces and perhaps also to that crossing the blood-brain barrier, diffusing through the brain and then concentrating on brain receptor sites. In our preliminary abstract we reported that kidney and liver concentrations in rabbits and dogs exceeded plasma levels but noted no pattern of relationship between tissue and plasma concentrations. However, we have observed that when hyperinsulinism persists, as in a dexamethasone-treated dog or hyperphagic, obese rodents, the insulin content of some organs, particularly the kidney, does reflect plasma levels. In rats and mice, the insulin concentrations in kidney extracts appear to increase linearly with plasma levels. Liver and heart insulin concentrations initially appear to increase with plasma but then plateau, suggesting a saturable mechanism. We believe that insulin extractable from tissues reflects binding of insulin to receptors and that the total content of insulin receptors in a tissue may be the sum of unoccupied receptor sites, as measured in receptor assays, and the sites occupied by insulin extractable from the tissue.