Measurement of interstitial insulin in human muscle

Previous measurements in lymph and adipose tissue have indicated that inter stitial insulin concentrations are similar to 40% lower than in plasma. Mea surements of insulin in human muscle interstitial fluid have not been perfo rmed yet. We developed a new external reference technique for calibration o f microdialysis catheters in situ. This technique allows correct assessment s of interstitial peptide concentrations and was employed to estimate the i nsulin concentration in medial quadriceps femoris muscle in II individuals (age: 37 +/- 3 yr; body mass index: 25.2 +/- 1.2 kg/m(2)) during a two-step euglycemic hyperinsulinemic clamp. At steady-state insulin and glucose inf usion, plasma glucose was 5.9 +/- 0.2 mmol/l, plasma insulin was 155 +/- 17 mU/l, and interstitial muscle insulin was 67 +/- 19 mU/l (n = 9; P < 0.01) . At a higher insulin infusion rate, the steady-state plasma insulin concen tration was 379 +/- 58 mU/l, and interstitial insulin concentration was 180 +/- 40 mU/l (P < 0.01). The data show for the first time that high physiol ogical and supraphysiological plasma insulin levels give 30-50% lower inter stitial concentrations of insulin in the muscle. The importance of capillar y delivery as a rate-limiting step for the insulin effect is suggested.