Minimal influence of blood flow on interstitial glucose and lactate-normal and insulin-resistant muscle

To study the regulation of the interstitial glucose concentration in skeletal muscle, nine control subjects and nine older and overweight non-insulin-dependent diabetes mellitus (NIDDM) subjects with extreme insulin resistance were investigated with microdialysis in the medial femoral muscle before and during a euglycemic insulin clamp. After an overnight fast, arterial plasma glucose concentration was 4.9 +/- 0.1 and 8.5 +/- 0.6 mmol/l (P < 0.001), respectively. The arterial-interstitial concentration ([a-i]) differences of glucose and lactate were 0.43 +/- 0.16 (P < 0.05) and -0.13 +/- 0.05 mmol/l, respectively, in normal subjects. In NIDDM subjects, [a-i] differences for glucose and lactate were nonsignificant. Muscle blood flow was similar in controls and NIDDM subjects. During the glucose clamp, the glucose [a-i] differences increased and the lactate [a-i] differences decreased significantly in both groups. The glucose 170 infusion rate was 8.0 +/- 0.77 vs. 3.2 +/- 0.51 mg.kg-1.min-1 (P < 0.001), and blood flow was 9.9 +/- 1.6 vs. 6.7 +/- 0.9 ml.100 g-1.min-1 (P < 0.05) in controls and NIDDM subjects, respectively. These results show that 1) the capillary wall is rate limiting for muscle glucose uptake and lactate release in control subjects but not in postabsorptive hyperglycemic insulin-resistant subjects, 2) vasodilation during insulin infusion does not prevent the increase in [a-i] difference of glucose in normal subjects, and 3) in severely insulin-resistant muscle, the [a-i] difference of glucose is not extended despite lack of vasodilation.