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 s keletal muscle, nine control subjects and nine older and overweight no n-insulin-dependent diabetes mellitus (NIDDM) subjects with extreme in sulin resistance were investigated with microdialysis in the medial fe moral muscle before and during a euglycemic insulin clamp. After an ov ernight fast, arterial plasma glucose concentration was 4.9 +/- 0.1 an d 8.5 +/- 0.6 mmol/l (P < 0.001), respectively. The arterial-interstit ial 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 norma l subjects. In NIDDM subjects, [a-i] differences for glucose and lacta te were nonsignificant. Muscle blood flow was similar in controls and NIDDM subjects. During the glucose clamp, the glucose [a-i] difference s 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 NIDD M subjects, respectively. These results show that 1) the capillary wal l is rate limiting for muscle glucose uptake and lactate release in co ntrol subjects but not in postabsorptive hyperglycemic insulin-resista nt 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.