ANTIBODY-SUPPRESSIBLE AND NONSUPPRESSIBLE INSULIN-LIKE ACTIVITIES IN HUMAN SERUM AND THEIR PHYSIOLOGIC SIGNIFICANCE. AN INSULIN ASSAY WITH ADIPOSE TISSUE OF INCREASED PRECISION AND SPECIFICITY*

Abstract

An adipose tissue assay for serum insulin-like activity (ILA) is described that makes use of glucose uptake and net gas exchange as metabolic indexes. Owing to a tissue pool design of 12 rats per assay, satisfactory precision was obtained. Upon serum dilution, there was a proportional decrease of serum ILA, provided that the values of net gas exchange were corrected for increased CO2 retention in undiluted serum. Results of serum ILA from both metabolic indexes correlated well. Serum diluted 1:5 appeared to influence these two metabolic indexes in a similar manner as crystalline insulin. Only 7% of total serum ILA of normal fasting subjects was suppressed by anti-insulin serum. Upon iv injection of regular insulin to normal subjects, suppressible ILA rose, whereas nonsuppressible ILA did not change. Oral and iv glucose administration led to a rise of suppressible ILA that was related in magnitude to the blood sugar level. In most serum samples of six patients with active [beta]-islet-cell adenoma, suppressible ILA was elevated and nonsuppressible ILA was normal In patients with untreated diabetes mellitus of recent onset, suppressible ILA was higher than in fasting normal subjects, but much lower than in normal subjects at comparable blood sugar levels. Suppressible ILA was not detected in patients in diabetic coma who had normal levels of nonsuppressible ILA. Preliminary evidence suggests that non-suppressible ILA affects adipose tissue metabolism in a way similar to crystalline insulin, that it is less effective in vivo than in vitro, or ineffective, and that it may closely be related to the insulin molecule.