In rats with uncontrolled DM induced by streptozotocin , UT-A1 urea transporter and AQP2 water channel abundances in the collecting duct were significantly increased after days after streptozotocin injection 16 - 18 , suggesting that these transporter proteins are up-regulated during DM-induced osmotic diuresis in order to prevent a serious volume depletion. On the other hand, vasopressin rapidly increases the phosphorylation of UT-A1 19 and is known to be elevated in DM 20 , 21 , which bring the thought that the increase of UT-A1 abundance in diabetic rats may be due to their high plasma vasopressin level.
To explore the effect of vasopressin on UT-A1 abundance in diabetic rats, Brattleboro rats which lack circulating vasopressin were infused with vasopressin or made diabetic by streptozotocin injection or received both procedures together DM for 10 days did not increase UT-A1 abundance in Brattleboro rats devoid of vasopressin, while vasopressin infusion for 12 days did significantly increase UT-A1 abundance, compared to untreated Brattleboro rats.
DM combined with vasopressin infusion had more increase in UT-A1 abundance over vasopressin infusion alone. These results suggest that vasopressin is necessary for the increase of UT-A1 abundance during diabetes. It is also suggested that a factor other than vasopressin is responsible for the increase in UT-A1 protein abundance because the same amount of vasopressin was administered to the two vasopressin treated groups of Brattleboro rats The ongoing osmotic diuresis due to non-reabsorbable glucose causes water to be retained in the tubule lumen which dilutes the urine urea concentration.
Several urea-specific signaling pathways have been identified in cultured mIMCD3 cells and the renal medulla 23 , 24 , suggesting the possibility that changes in the percentage or concentration of urea in the urine or medullary interstitium could be a factor that regulates UT-A1 protein abundance.
The urine urea concentration in this group was significantly increased when compared to that of diabetic rats with regular diet, although it was reduced when compared to control. UT-A1 abundance did not change in urea fed diabetic rats, which suggests that the increase of UT-A1 in diabetic rats is due to the decrease of urea in the urine Usually, low urine urea concentrations and low urine osmolalities occur simultaneously, making it difficult to know which one is responsible for an increase in UT-A1 abundance.
However, these two conditions can be dissociated if total urinary solute is increased by urea itself. UT-A2 and UT-B mediate intra-renal urea recycling through the thin descending limb and descending vasa recta, respectively 26 , UT-A2 is up-regulated in UT- B knock-out mice, suggesting that loss of one urea recycling pathway can be partially compensated for by increasing the other pathway UT-A2 and UT-B abundances were increased in urea diuresis 25 , where the urine urea concentration increased, but was unchanged or decreased in NaCl diuresis and DM-induced glucose diuresis 18 , 25 , where the urine urea concentration is low.
This suggests that UT-A2 and UT-B abundances increase when the medullary interstitial urea concentration is high, which would tend to increase intra-renal urea recycling during antidiuresis, thereby preventing the loss of urea from the medulla and maintaining medullary interstitial osmolality Vesicular transport as a new paradigm in short-term regulation of transepithelial transport. Renal Sodium Transporters and Water Channels.
Korean Association of Medical Journal Editors. E-mail: koreamed kamje. Electrolyte Blood Press. Published online March 31, Corresponding author: Dong-Un Kim, M.
Tel: , Fax: , Email: dukim catholic. Dong-Un Kim, M. The urea transporter family. Urine concentration. Intra-renal urea recycling. Long term regulation of urea transporters.
Urea transporters in kidney and erythrocytes. When the papillary interstitial urea concentration is low, urea secretion into the thin Henle is minimal. Thick Henle and Distal Convoluted Tubule These segments are highly impermeable to urea and given the large amounts of water resorption in these segments, urea becomes increasingly concentrated within the tubule.
Collecting Ducts The medullary portion of the collecting ducts display the highest levels of permeability to urea. Ultimately, the reason why urea is more concentrated in the renal medulla, and thus contributes to the corticopapillary osmotic gradient, is two fold: 1 The distal portion of the collecting ducts is highly urea-permeable, 2 Tubular urea is the most concentrated in this segment and thus there is the largest driving force for passive urea resorption in the distal collecting ducts.
However, the permeability of the medullary collecting ducts can significantly increase in the presence of ADH. In the presence of ADH, specific urea transporters are placed on the tubular epithelial cell membrane in this segment, rendering it more urea-permeable.
Regulation of Urea Resorption Overview The primary locus at which urea transport is regulated is the medullary section of the collecting ducts. The ultimate amount of urea resorbed in the collecting ducts is dependent on the permeability and the tubular concentration of urea in this segment. Both of these factors are affected by the presence of ADH. ADH Absent When ADH is absent the volume of water in the tubule is relatively high in the distal collecting duct, thus diluting the concentration of tubular urea and making the driving force for passive resorption of urea low.
In addition, in the absence of ADH the medullary collecting tubule permeability to urea is less. Together, these factors combine to reduce urea resorption in the distal collecting duct and lessen the contribution of urea to the corticopapillary osmotic gradient.
ADH Present In the presence of ADH, water volume is avidly resorbed in the distal tubule and thus urea becomes highly concentrated, generating a large driving force passive urea resorption. As discussed above, the presence of ADH also renders the medullary collecting ducts highly permeable to urea. Together, these factors result in large amounts of urea being resorbed from the medullary collecting ducts and thus contributing to the corticopapillary osmotic gradient.
Therefore there will be more diffusion of urea into the medulla out of the cortical duct, and therefore the fluid in the thin limbs of the loop of Henle will become more concentrated along its journey through the medulla. In short, this mechanism increases the efficiency of water removal from the tubular fluid, and contributed to the defence of volume and osmolality. With these steps, even humans can achieve a urinary concentration of urea which is almost times the plasma concentration.
If this renal-flavored chapter is not the right place to talk about the metabolic relevance of urea, then to discuss glucose is even further out of the question. Let us limit ourselves to soberly noting that glucose is a hexose monosaccharide sugar which is naturally most abundant as its D-stereoisomer, giving rise to the term "dextrose".
It has a molar mass of Daltons three times higher than urea and its pKa is about 12, which means it does not dissociate at physiological pH. It is a polar molecule, not protein bound, and dissolves in lipid with only the greatest reluctance. All of this means that in the nephron this little molecule should be expected to filter effortlessly through the glomerulus and then require specific transport mechanisms to reclaim it from the urine.
And it is essential to reclaim it. Unlike urea, the role of which is purely excremento-janitorial, glucose has the noble task of rewarding the human organism with energy. Obviously this does not happen. The reason for your puzzling failure to excrete an entire cake worth of sugar every day is the tireless work of proximal tubular transporters which keep reabsorbing glucose at the same rate as it is filtered. Both leverage the sodium gradient to co-transport glucose out of the lumen and into the proximal tubule cells.
From there, it diffuses passively though GLUT channels and is reclaimed by the peritubular capillaries. This reabsorption process is saturable.
It appears that under normal circumstances i. As glomerular filtration rate decreases, so the reabsorptive capacity of the remaining functional nephrons seems to suffer, and glycosuria develops with a progressively lower BSL, or so it is thought.
Weirdly, increasing the glomerular filtration rate also increases the threshold - i. The precise mechanism which explains this renal glucose reabsorption threshold is unknown, and moreover people are not entirely convinced there even is such a threshold, as glucose is still found in the urine even at normal BSL values Wolf et al, Klein, Janet D.
Blount, and Jeff M. Weiner, I. David, William E. Mitch, and Jeff M. Bankir, Lise, and Baoxue Yang. Bankir, Lise, et al. Johnson, W. Rudman, Daniel, et al. Ullrich, Karl J. Gottschalk, C.
Micropuncture study of composition of loop of Henle fluid in desert rodents. Am J Physiol : Lassiter, William E. Gottschalk, and Margaret Mylle. Pennell, J. Phillip, Frank B. Lacy, and Rex L. Stewart, John. Sands, Jeff M.
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