These studies were undertaken to determine the distribution of insulin between the intravascular and interstitial compartments in 19 nondiabetic and 16 high-dose (60 mg/kg) STZ-induced diabetic rats. Anesthetized male rats underwent cannulation of the thoracic lymph duct with continuous collection of lymph by passive drainage; 90-min hyperinsulinemic (0, 14, 28, or 42 pmol · kg−1 · min−1) glucose clamps were performed with serum glucose held at the preinfusion level. Integrated lymph samples were collected, with serum collection at the midpoint. Before insulin infusion, insulin levels in lymph as a percentage of levels in serum were higher in the diabetic rats (lymph = 103 ± 8% of 52 matched serum values, mean ± SE) compared with nondiabetic rats (lymph = 83 ± 3% of serum; n = 84, P < 0.008). Under steady-state conditions during insulin infusion (66-90 min), lymph insulin as a percentage of serum insulin decreased significantly in nondiabetic animals (range 53-62% in all insulin-infused groups, vs. 94% in the absence of insulin infusion, P < 0.0001). However, in the diabetic animals, the proportion was similar in the presence or absence of infused insulin (range 57–63% in insulin-infused groups vs. 70% in the absence of infused insulin, P = NS). Lymph flow rate was significantly higher in diabetic than nondiabetic rats (37.7 ± 7.2 vs. 17.9 ± 1.5 microliters/min [mean ± SE], P < 0.02). Distribution of [14C]inulin was uniform between the two compartments in all animals. In nondiabetic rats, correlation of lymph and serum levels of insulin with hepatic glucose output was equal(r = −0.86 and −0.85 for serum and lymph insulin, respectively) and as was the case for peripheral glucose disposal, r = 0.75 for serum, and r = 0.72 for lymph. Estimated clearance of insulin from serum to lymph was 100% higher in the diabetic rats (22.9 vs.12.7 µl/min). The mechanism is unclear but may represent increased transcapillary transport of insulin, adaptive to insulin deficiency.

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