IMPORTANCE OF TRANSCAPILLARY INSULIN TRANSPORT TO DYNAMICS OF INSULINACTION AFTER INTRAVENOUS GLUCOSE

Insulin action in vivo is determined by both transendothelial insulin transport (TET) across the capillary and subsequent insulin binding an d postreceptor events. To examine TET under non-steady-state condition s, 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 in jection, dynamics of glucose in plasma and lymph were similar, suggest ing 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 re mained lower than plasma insulin throughout the IVGTT (P < 0.05 or bet ter). Minimal model-derived insulin sensitivity (S-I) averaged 3.55 +/ - 0.75 x 10(-4) min(-1)/(mu U/ml). There was a strong linear relations hip 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 th at cellular sensitivity to interstitial insulin dominated (r(2) = 0.55 ), but was not the exclusive determinant of, overall S-I, as insulin t ransport was also important (r(2) = 0.21). TET is a previously unrecog nized contributor to S-I in vivo.