These studies test, using intravital microscopy (IVM), the hypotheses that perfusion effects on insulin-stimulated muscle glucose uptake (MGU) are 1) capillary recruitment independent and 2) mediated through the dispersion of glucose rather than insulin. For experiment 1, capillary perfusion was visualized before and after intravenous insulin. No capillary recruitment was observed. For experiment 2, mice were treated with vasoactive compounds (sodium nitroprusside, hyaluronidase, and lipopolysaccharide), and dispersion of fluorophores approximating insulin size (10-kDa dextran) and glucose (2-NBDG) was measured using IVM. Subsequently, insulin and 2[14C]deoxyglucose were injected and muscle phospho-2[14C]deoxyglucose (2[C14]DG) accumulation was used as an index of MGU. Flow velocity and 2-NBDG dispersion, but not perfused surface area or 10-kDa dextran dispersion, predicted phospho-2[14C]DG accumulation. For experiment 3, microspheres of the same size and number as are used for contrast-enhanced ultrasound (CEU) studies of capillary recruitment were visualized using IVM. Due to their low concentration, microspheres were present in only a small fraction of blood-perfused capillaries. Microsphereperfused blood volume correlated to flow velocity. These findings suggest that 1) flow velocity rather than capillary recruitment controls microvascular contributions to MGU, 2) glucose dispersion is more predictive of MGU than dispersion of insulin-sized molecules, and 3) CEU measures regional flow velocity rather than capillary recruitment.
|Original language||English (US)|
|Journal||American Journal of Physiology - Endocrinology and Metabolism|
|State||Published - 2019|
Bibliographical noteFunding Information:
This study was funded by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-059637, DK-054902, DK-050277, T32-DK-101003, F32-DK-120104, and P30-DK-020593 and the American Heart Association Peripheral Artery Disease Strategically Focused Research Network at Vanderbilt University.
Copyright © 2019 the American Physiological Society.
- Capillary recruitment
- Insulin resistance
- Intravital microscopy