Importance of transcapillary insulin transport to dynamics of insulin action after intravenous glucose

Abstract

Insulin action in vivo is determined by both transendothelial insulin transport (TET) across the capillary and subsequent insulin binding and postreceptor events. To examine TET under non-steady-state conditions, we performed intravenous glucose tolerance tests (IVGTT; 0.3 g/kg; n = 7) on conscious dogs. At basal, insulin in lymph was only 53 +/- 7% of plasma insulin (P < 0.001), whereas lymph glucose exceeded plasma levels (109 +/- 4 vs. 104 +/- 4 mg/dl, respectively; P < 0.02). On injection, dynamics of glucose in plasma and lymph were similar, suggesting rapid equilibration of glucose between compartments. In contrast, insulin appearance in lymph was delayed relative to plasma (5.1 +/- 1.3 vs. 2 +/- 0 min), peaked later (21 +/- 2 vs. 8 +/- 2 min), attained peak value of only 52 +/- 6% of plasma insulin (range, 35-76%), and remained lower than plasma insulin throughout the IVGTT (P < 0.05 or better). Minimal model-derived insulin sensitivity (SI) averaged 3.55 +/- 0.75 x 10(-4) min-1/(microU/ml). There was a strong linear relationship between lymph insulin and its effect on glucose disappearance [X(t), r = 0.95 +/- 0.01]. Determination of the relative contributions of TET and post-TET insulin-sensitive processes to overall SI revealed that cellular sensitivity to interstitial insulin dominated (r2 = 0.55), but was not the exclusive determinant of, overall SI, as insulin transport was also important (r2 = 0.21). TET is a previously unrecognized contributor to SI in vivo.