Increased Transcapillary Escape Rate of Albumin in Nondiabetic Men in Response to Hyperinsulinemia

Diabetic patients manifest increased vascular permeability. To determine whether insulin per se might increase vascular permeability, five nondiabetic men were studied by the hyperinsulinemic-euglycemic clamp technique. Each subject received a 0.72-nmol/kg body wt i.v. insulin bolus, followed by a 72-pmol · kg−1 ·min−1 insulin infusion for 4 h. Euglycemia was maintained by the Biostator glucose controller. At 7 h of study, 10 μCi i.v. 125I-labeled albumin was injected as bolus dose. Frequent blood samples were drawn during the next 70 min for determination of the transcapillary escape rate (TER) of albumin. Subjects returned 1–2 wk later for a control study, during which 0.45% saline was infused at a rate identical to the dextrose and insulin infusion rates during the hyperinsulinemic clamp. The mean ± SE serum insulin levels during the hyperinsulinemic clamp and saline infusion were 9786 ± 126 and 46 ± 4 pM, respectively, whereas serum glucose during the two sessions was similar (5.0 ± 0.2 vs. 4.8 ± 0.1 mM, NS). Identical fluid volumes were infused during the two sessions (1767 ± 197 ml/7 h), and urine outputs did not differ significantly (1615 ± 309 vs. 1035 ± 248 ml/7 h). The TER of albumin was greater in all five men after hyperinsulinemia than after saline infusion (18.3 ± 2.7 vs. –2.8 ± 2.3%/h, P = 0.01). The serum albumin level at the end of the hyperinsulinemic-euglycemic clamp study was 14% lower than the value at the start of the study (37 ± 1 vs. 42 ± 1 g/L, P 0.05), whereas no significant change in serum albumin levels occurred during the saline infusion. These observations suggest that acute hyperinsulinemia can increase the TER of radiolabeled albumin, probably by increasing vascular permeability.