Since anaerobic glycolysis yields two lactates for each glucose consumed and is the main source of ATP for IM cell maintenance, we propose glycolysis as a likely source of "external" IM osmoles. It has long been known that such an osmole source could contribute to the concentrating "single-effect." We also suggest that the importance of the resulting axial osmotic gradient would depend on IM vasa recta (VR) blood flow, which varies with the animal's diuretic state.
We used numerical simulation to estimate axial gradients of lactate and glucose that could accumulate by countercurrent recycling in IM vasa recta. We assumed a constant glycolytic rate per nl of cell volume (no reason why IM metabolic rate should depend on diuretic state). Axial loop- and VR-distribution and IM tissue mass were according to reported values for rat and other rodents. Lactate and glucose permeabilities were varied over a range of likely values.
According to our calculations, less than 1% of glucose delivered to IM is consumed and this could suffice to build an important steady state axial osmotic gradient. For the hydropenic rat, we predict lactate + glucose osmoles at the papillary tip to be about 20 mOsm, and halving the VR inflow rate, as in antidiuresis, could (depending on lactate permeability) push this up to around 140 mOsm. It has been shown by us and by others (Jen & Stephenson, 1994, Bull. Math. Biol. 56:491-514; Thomas & Wexler, 1995, Am. J. Physiol. 269:F159-F171) that this level of external osmolytes would greatly improve IM concentrating ability. We explore several other scenarios and conclude that glycolytic osmole production could reasonably play an important role in the concentrating mechanism.