The human forearm was used as a model system for testing the biological activity of proinsulin (PI) upon peripheral adipose tissue and muscle. Contrasts were made with equimolar perfusions of single component insulin (SCI) in a mean venous perfusion concentration of 263 μU per milliliter and also with SCI perfusions giving venous concentrations of 83 or 47.7 μU permilliliter. Mean venous concentration of PI when perfused alone was equivalent on a molar basis to SCI at 281 μU. per milliliter. PI, at a molar excess of 26:1 (PI:endogenous insulin), shut off lipolysis and promoted potassium uptake but was only slightly effective in promoting glucose uptake. PI was quantitatively similar in effect to 47.7 or 83 μU. per milliliter of insulin upon K flux and blockade of lipolysis but less effective than 47.7 μU. per milliliter in promotion of glucose uptake. When PI and SCI were simultaneously perfused in a molar ratio of 1:1, PI neither augmented nor inhibited SCI actions.

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