Transport of peptide hormones across isolated rat mesentery: effect of human serum-bound insulin.
The exchange of 125I-insulin, 125I-glucagon, 125I-proinsulin, 125I-growth hormone, 131I-albumin, 14C-inulin, and 14C-dextran across isolated rat mesentery was studied in a diffusion cell. The passage of immunoprecipitable porcine 125I-insulin (0.88 ng./ml.) was not affected by porcine proinsulin (145 ng./ml.), crystalline porcine insulin (17.4 ng./ml.), human growth hormone (87 ng./ml.), bovine serum albumin (4.5 mg./ml.), or normal guinea pig serum (840 mug. protein/ml.). However, the rate of insulin exchange was reduced by guinea pig anti-insulin antiserum and partially purified human serum-bound insulin (175 mug. protein/ml.). Bound insulin at the same concentration did not affect the exchange of 125I-glucagon, 125I-growth hormone, 14C-inulin, or 14C-dextran. Further purification of bound insulin by Sephadex G-100 chromatography yielded an approximately 45,000-molecular-weight fraction that at 5 mug. protein permilliliter allowed essentially no insulin transport. This same fraction of bound insulin significantly inhibited the disappearance of immunoprecipitable porcine 125I-insulin from the incubation medium of isolated rat hemidiaphragms. Theses studies suggest that the transport of insulin across biologic membranes, mesothelium, and possible endothelium is specifically inhibited by bound insulin, a circulating macromolecule that possesses insulin-like activity.