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Contraction stimulates nitric oxide independent microvascular recruitment and increases muscle insulin uptake

¹Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA 22908

Correspondence: ejb8x{at}virginia.edu

Key Words: Exercise-muscle contraction • nitric oxide • insulin uptake • capillary recruitment

Objective:We examined whether contraction-induced muscle microvascular recruitment would expand the surface area for insulin and nutrient exchange and thereby contribute to insulin-mediated glucose disposal.

Design/Methods and Results:We measured in vivo rat hindlimb microvascular blood volume (MBV) using contrast ultrasound and femoral blood flow (FBF) using Doppler ultrasound in response to a stimulation frequency range. Ten min of 0.1 Hz isometric contraction more than doubled MBV (P< 0.05; n=6) without affecting FBF (n=7), while frequencies >0.5 Hz increased both. Specific inhibition of nitric-oxide (NO) synthase with L-NAME (n=5) significantly elevated mean arterial pressure by 30 mmHg but had no effect on basal FBF or MBV. We next examined whether selectively elevating MBV without increasing FBF (0.1 Hz contractions) increased muscle uptake of albumin-bound Evans Blue dye (EBD). Stimulation at 0.1 Hz (10 min) elicited > 2-fold increases in EBD content (ug EBD/g dry tissue) in stimulated vs contralateral muscle (n=8; 52.2 ± 3.8 vs 20.0 ± 2.5; P< 0.001). We then measured muscle uptake of EBD and ¹²⁵I-insulin (dpm/g dry tissue) with 0.1 Hz stimulation (n=6). Uptake of EBD (19.1 ± 3.8 vs 9.9 ± 1.0; P< 0.05) and ¹²⁵I-insulin (5300 ± 800 vs 4244 ± 903; P< 0.05) was greater in stimulated vs control.

Conclusion:low-frequency contraction increases muscle MBV by a NO-independent pathway and facilitates muscle uptake of albumin and insulin in the absence of blood flow increases. This microvascular response may, in part, explain enhanced insulin action in exercising skeletal muscle.

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