title: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Southern California, Los Angeles 90033.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Yang
authors.forename: I D
authors.initials: ID
authors.lastname: Hope
authors.forename: M
authors.initials: M
authors.lastname: Ader
authors.forename: R N
authors.initials: RN
authors.lastname: Bergman
mesh_terms: D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D002199:Capillary Permeability; D004285:Dogs; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007275:Injections, Intravenous; D007328:Insulin / Q000378:metabolism* / Q000502:physiology*; D008196:Lymph / Q000378:metabolism; D008297:Male
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose