Effect of metabolic acidosis on glucose reabsorption in rats with acute hyperglycemia

1990 ◽  
Vol 68 (1) ◽  
pp. 79-83 ◽  
Author(s):  
P. O. Magner ◽  
M. L. Halperin
Keyword(s):  
Proximal Tubule ◽  
Fractional Excretion ◽  
Electrochemical Gradient ◽  
Osmotic Diuresis ◽  
Acute Hyperglycemia ◽  
Luminal Membrane ◽  
Glucose Reabsorption ◽  
Other Substances ◽  
Hyperglycemic Hyperosmolar Nonketotic Coma ◽  
Filtered Load

The rate of reabsorption of glucose in the kidney is a factor to consider with respect to the degree of hyperglycemia in poorly controlled diabetics. The rate of reabsorption of glucose in the proximal tubule is driven by the electrochemical gradient for sodium across the luminal membrane. This gradient in the proximal tubule is also used to reabsorb a number of other substances, quantitatively the most important being bicarbonate. We wished to explore the hypothesis that acidosis, by reducing the filtered load of bicarbonate and therefore the reabsorption of bicarbonate in the proximal tubule, might permit an increased rate of reabsorption of glucose. Hyperglycemia was induced in rats by the infusion of hypertonic glucose. Reabsorption of glucose was measured by clearance methods and factored for glomerular filtration rate (GFR), which has a direct effect on the reabsorption of glucose. The reabsorption of glucose was increased in the kidney when the reabsorption of bicarbonate in the proximal tubule was decreased by either HCl-induced acidosis or the administration of a carbonic anhydrase inhibitor. This effect was independent of a change in GFR and the fractional excretion of Na, factors that may also lead to changes in the reabsorption of glucose by the kidney.Key words: diabetes mellitus, hyperglycemic hyperosmolar nonketotic coma, diabetic ketoacidosis, proximal convoluted tubule, hyperglycemia, glucosuria, osmotic diuresis.

scholarly journals Role of KCNE1-Dependent K+ Fluxes in Mouse Proximal Tubule

2001 ◽  
Vol 12 (10) ◽  
pp. 2003-2011
Author(s):  
VOLKER VALLON ◽  
FLORIAN GRAHAMMER ◽  
KERSTIN RICHTER ◽  
MARKUS BLEICH ◽  
FLORIAN LANG ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Coupled Transport ◽  
Wild Type ◽  
Electrochemical Gradient ◽  
Volume Depletion ◽  
Luminal Membrane ◽  
Clearance Studies ◽  
Electrophysiological Studies ◽  
Kidney Micropuncture

Abstract. The electrochemical gradient for K+ across the luminal membrane of the proximal tubule favors K+ fluxes to the lumen. Here it was demonstrated by immunohistochemistry that KCNE1 and KCNQ1, which form together the slowly activated component of the delayed rectifying K+ current in the heart, also colocalize in the luminal membrane of proximal tubule in mouse kidney. Micropuncture experiments revealed a reduced K+ concentration in late proximal and early distal tubular fluid as well as a reduced K+ delivery to these sites in KCNE1 knockout (-/-), compared with wild-type (+/+) mice. These observations would be consistent with KCNE1-dependent K+ fluxes to the lumen in proximal tubule. Electrophysiological studies in isolated perfused proximal tubules indicated that this K+ flux is essential to counteract membrane depolarization due to electrogenic Na+-coupled transport of glucose or amino acids. Clearance studies revealed an enhanced fractional urinary excretion of fluid, Na+, Cl-, and glucose in KCNE1 -/- compared with KCNE1 +/+ mice that may relate to an attenuated transport in proximal tubule and contribute to volume depletion in these mice, as indicated by higher hematocrit values.

Effect of Phlorhizin on Renal Glucose and Phosphate Transport in the Dog

1979 ◽  
Vol 57 (4) ◽  
pp. 367-374 ◽  
Author(s):  
Sung-Feng Wen
Keyword(s):  
Proximal Tubule ◽  
Sodium Transport ◽  
Fractional Excretion ◽  
Phosphate Transport ◽  
Reciprocal Relationship ◽  
Sodium Reabsorption ◽  
Group I ◽  
Glucose Reabsorption ◽  
Fractional Excretion Of Sodium ◽  
Proximal Tubular

1. Clearance and micropuncture studies were performed in 19 thyroparathyroidectomized dogs to examine the inter-relationship between the renal transport of sodium, glucose and phosphate. 2. All experiments were carried out before and after the intravenous administration of phlorhizin [7 mg (15 μmol)/kg] with a sustaining infusion of the same dose/h. Thirteen dogs were studied during hydropenia (group I) and six dogs in the volume-expanded state (group II). 3. In the proximal tubule, phlorhizin significantly reduced sodium reabsorption in hydropenic dogs, but had no effect in volume-expanded dogs. Proximal tubular glucose reabsorption was completely inhibited by phlorhizin in both groups, but no significant change in phosphate reabsorption was observed. 4. Fractional glucose excretion in the urine reached 83–89% after phlorhizin, values significantly less than 100%, suggesting a residual reabsorption of glucose in a more distal segment or in deep nephrons. The changes in fractional excretion of sodium and phosphate were significantly correlated. 5. The effect of phlorhizin on both sodium and glucose reabsorption in the proximal tubule in hydropenic dogs suggests the existence of a co-transport mechanism, whereas the absence of an effect on sodium transport in volume-expanded dogs despite complete inhibition of glucose reabsorption indicates the existence of a sodium-independent component of net proximal tubular glucose transport. 6. Absence of the effect of phlorhizin on proximal tubular phosphate transport in the face of a significant reduction in sodium reabsorption implies that the reciprocal relationship between glucose and phosphate transport could be masked by the changes in sodium transport. Thus the sodium-phosphate transport relationship may prevail over that of glucose-phosphate in the proximal tubule.

scholarly journals SGLT2 Inhibitors: Physiology and Pharmacology

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0002772021
Author(s):  
Ernest M Wright
Keyword(s):  
Proximal Tubule ◽  
Glycosylated Hemoglobin ◽  
Blood Stream ◽  
Sglt2 Inhibitors ◽  
Luminal Membrane ◽  
Glucose Reabsorption ◽  
Lower Plasma Glucose ◽  
Glomerular Filtrate ◽  
Glucose Excretion

SGLTs are sodium glucose transporters found on the luminal membrane of the proximal tubule, where they reabsorb some 180 grams (one mole) of glucose from the glomerular filtrate each day. The natural glucoside phlorizin completely blocks glucose reabsorption. Oral SGLT2 inhibitors are rapidly absorbed into the blood stream where they remain in in the circulation for hours. On glomerular filtration, they bind specifically to SGLT2 in the luminal membrane of the early proximal tubule to reduce glucose reabsorption by 50-60%. Because of glucose excretion, these drugs lower plasma glucose and glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. The drugs also protect against heart and renal failure. The aim of this review is to summarize what is currently known about the physiology of renal SGLTs and the pharmacology of SGLT drugs.

Effect of luminal pH and HCO3- on phosphate reabsorption in the rabbit proximal convoluted tubule

1984 ◽  
Vol 247 (1) ◽  
pp. F25-F34
Author(s):  
L. L. Hamm ◽  
J. P. Kokko ◽  
H. R. Jacobson
Keyword(s):  
Proximal Tubule ◽  
Proximal Convoluted Tubule ◽  
Phosphate Reabsorption ◽  
Luminal Membrane ◽  
Glucose Flux ◽  
Glucose Reabsorption ◽  
All Solutions ◽  
Qualitative Effect ◽  
Phosphate Flux ◽  
Luminal Ph

Luminal pH in the proximal convoluted tubule may alter phosphate reabsorption in a variety of acid-base disturbances and in normal conditions as luminal pH decreases along the length of the proximal tubule. These studies address the influence of luminal pH on phosphate reabsorption in isolated perfused proximal convoluted tubules from normal rabbits. Initial perfusates were either pH 6.2 or 7.4, and the bath pH was 7.4. All solutions contained 10 mM total phosphate. The first experiments used HCO3-/CO2-free solutions to examine the effect of luminal pH independent of changes in [HCO3-] or Pco2. Lumen-to-bath phosphate flux increased from 0.63 +/- 0.23 with alkaline perfusate to 2.04 +/- 0.35 pmol X mm-1 X min-1 with acid perfusate. In a separate group of tubules, acetazolamide had no qualitative effect on this result. With HCO3-/CO2-containing solutions, phosphate reabsorption increased from 4.53 +/- 1.46 with alkaline perfusate to 9.67 +/- 1.77 pmol X mm-1 X min-1 with acid perfusate. Thus, an acid luminal fluid can enhance proximal phosphate reabsorption independent of the presence or absence of HCO3-/CO2. To examine the specificity of this effect, the influence of luminal pH on another solute (glucose), reabsorbed via a Na+-coupled mechanism, was studied. Lumen-to-bath glucose flux increased in the same direction: from 52.78 +/- 4.91 with alkaline perfusate to 57.13 +/- 4.70 pmol X mm-1 X min-1 with acid perfusate. The mechanism of the influence of luminal pH on phosphate and glucose reabsorption is not explained but could be direct or indirect from changes in intracellular pH, Na+ activity, metabolism, or basolateral transport. Since an acid luminal pH is expected to inhibit or decrease Na+-H+ exchange at the luminal membrane, these results are also consistent with a competition for the available Na+ gradient between phosphate and glucose transport and the Na+-H+ exchanger in the proximal tubule.

scholarly journals Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis

2004 ◽  
Vol 287 (1) ◽  
pp. R58-R68 ◽  
Author(s):  
Elisabete A. Dos Santos ◽  
Annette J. Dahly-Vernon ◽  
Kimberly M. Hoagland ◽  
Richard J. Roman
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
Brush Border ◽  
Fractional Excretion ◽  
Renal Perfusion ◽  
Inhibitory Effects ◽  
Sodium Hydrogen Exchanger ◽  
Pressure Natriuresis ◽  
Cytochrome P 450 ◽  
Filtered Load

This study examined the effects of chronic blockade of the renal formation of epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid with 1-aminobenzotriazole (ABT; 50 mg·kg−1· day−1 ip for 5 days) on pressure natriuresis and the inhibitory effects of elevations in renal perfusion pressure (RPP) on Na+-K+-ATPase activity and the distribution of the sodium/hydrogen exchanger (NHE)-3 in the proximal tubule of rats. In control rats ( n = 15), sodium excretion rose from 2.3 ± 0.4 to 19.4 ± 1.8 μeq·min−1·g kidney weight−1 when RPP was increased from 114 ± 1 to 156 ± 2 mmHg. Fractional excretion of lithium rose from 28 ± 3 to 43 ± 3% of the filtered load. Chronic treatment of the rats with ABT for 5 days ( n = 8) blunted the natriuretic response to elevations in RPP by 75% and attenuated the increase in fractional excretion of lithium by 45%. In vehicle-treated rats, renal Na+-K+-ATPase activity fell from 31 ± 5 to 19 ± 2 μmol Pi·mg protein−1·h−1 and NHE-3 protein was internalized from the brush border of the proximal tubule after an elevation in RPP. In contrast, Na+-K+-ATPase activity and the distribution of NHE-3 protein remained unaltered in rats treated with ABT. These results suggest that cytochrome P-450 metabolites of arachidonic acid contribute to pressure natriuresis by inhibiting Na+-K+-ATPase activity and promoting internalization of NHE-3 protein from the brush border of the proximal tubule.

Dissociation of proximal tubular glucose and Na+ reabsorption by amphotericin B

1979 ◽  
Vol 236 (4) ◽  
pp. F392-F397
Author(s):  
P. S. Aronson ◽  
J. P. Hayslett ◽  
M. Kashgarian
Keyword(s):  
Proximal Tubule ◽  
Glucose Uptake ◽  
Amphotericin B ◽  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Na Transport ◽  
Glucose Reabsorption ◽  
Tubular Lumen ◽  
Proximal Tubular ◽  
Necturus Proximal Tubule

The effect of amphotericin B on glucose and Na+ transport was studied in the Necturus proximal tubule and in microvillus membrane vesicles isolated from the rabbit renal cortex. In the Necturus experiments, the rate constants for disappearance of radiolabeled glucose (kG) and mannitol (kM) from the tubular lumen were determined by stop-flow microperfusion. Saturability and Na+-dependence of glucose reabsorption was confirmed, since kG was reduced by raising intratubular glucose from 1 to 5 mM or by replacing intratubular Na+ with choline. Neither maneuver affected kM. Intratubular amphotericin B (10 microgram/ml), previously shown to stimulate active Na+ reabsorption in the Necturus proximal tubule, inhibited kG with no effect on kM. In the membrane vesicle preparation, amphotericin inhibited the uphill glucose uptake which results from imposing a NaCl gradient from outside to inside, but had no effect on glucose uptake in either the absence of Na+ or in the presence of Na+ when there was no Na+ gradient. Amphotericin B stimulated the uptake of Na+ by the vesicles. The observed dissociation of glucose and Na+ transport by amphotericin B is consistent with the concept that proximal tubular glucose reabsorption is energized by the luminal membrane Na+ gradient and is not directly linked to active Na+ transport per se.

Studies of the urinary acidification defect induced by lithium

1982 ◽  
Vol 242 (1) ◽  
pp. F23-F29 ◽  
Author(s):  
N. Bank ◽  
P. D. Lief ◽  
H. S. Aynedjian ◽  
B. F. Mutz
Keyword(s):  
Proximal Tubule ◽  
Renal Tubular Acidosis ◽  
Electrical Potential ◽  
Distal Renal Tubular Acidosis ◽  
Distal Nephron ◽  
Luminal Membrane ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Convoluted Tubules

Experiments were carried out in rats and isolated turtle bladders to study the defect in H+ transport induced by LiCl. After 3-4 days of intraperitoneal LiCl, rats developed urinary findings of "distal" renal tubular acidosis. Proximal tubular fluid pH measured in situ by glass microelectrodes was higher in lithium-treated rats than in acidotic controls. Proximal fluid total CO2 [tCO2] was also higher, and the fraction of tCO2 leaving the proximal tubule was 14 vs. 7% (P less than 0.001). Impaired acidification was also apparent beyond distal convoluted tubules, as judged by normal distal tCO2 reabsorption but increased HCO3(-) in the urine. During NaHCO3 loading, the proximal defect was ameliorated but not the distal. Turtle bladder studies showed that mucosal lithium inhibits H+ secretion secondary to reducing transepithelial electrical potential, presumably by hyperpolarization of the luminal membrane. A similar mechanism may be responsible for lithium's effect on the distal nephron. Inhibition of proximal tubular HCO3(-) reabsorption is probably not attributable to electrical potential changes but might be due to interference of luminal membrane Na+ entry by Li+ and reduced (Na+ + Li+)-H+ exchange.

Effect of norepinephrine on cellular sodium transport in Ambystoma kidney proximal tubule

1994 ◽  
Vol 267 (5) ◽  
pp. F725-F736 ◽  
Author(s):  
S. Abdulnour-Nakhoul ◽  
R. N. Khuri ◽  
N. L. Nakhoul
Keyword(s):  
Proximal Tubule ◽  
Ambystoma Tigrinum ◽  
Na Transport ◽  
Control Solution ◽  
Kidney Proximal Tubule ◽  
Luminal Membrane ◽  
Intracellular Na Activity ◽  
Beta Receptors ◽  
Membrane Potential Difference ◽  
External K

The effect of norepinephrine (NE) on mechanisms of cellular Na+ transport in the isolated, perfused proximal tubule of Ambystoma tigrinum was examined. Single-barreled voltage and ion-selective microelectrodes were used to determine basolateral (V1), luminal (V2), and transepithelial (V3) membrane potentials and intracellular Na+ activity (alpha Nai). In CO2/HCO3- control solution, addition of NE (10(-6) M) to the bath caused depolarizations of V1, V2, and V3 are decreased alpha Nai. These effects were mimicked by isoproterenol and inhibited by propranolol. Addition of NE in the absence of luminal Na+ and substrates did not cause any changes in V1, V2, V3, or alpha Nai. NE did not affect the changes in membrane potential difference (PD) or alpha Nai caused by removal and readdition of luminal substrates and/or Na+. To study the effect of NE on Na-K-adenosinetriphosphatase (Na-K-ATPase), the pump was inhibited by external K+ removal and then reactivated by readdition of 12 mM K+ to the bath in the presence and absence of NE. Reactivation of the pump caused hyperpolarization of membrane PDs, and alpha Nai recovered monotonically in 3-5 min. The peak hyperpolarizations of V1 and V2 (approximately 1 min) were significantly larger in the presence of NE. During the first 3 min, and also at the same alpha Nai, the rate of decrease of alpha Nai was significantly faster in the presence of NE. In conclusion, these results show a direct effect of NE on cell membrane PDs and alpha Nai in the kidney proximal tubule. Most likely, beta-receptors are involved in mediating the action of NE. Neither Na/H exchange nor Na-substrate cotransport at the luminal membrane are affected by NE. On the other hand, NE activates Na-K-ATPase.

NHE3 activity and trafficking depend on the state of actin organization in proximal tubule

2001 ◽  
Vol 280 (2) ◽  
pp. F283-F290 ◽  
Author(s):  
C. Chalumeau ◽  
D. Du Cheyron ◽  
N. Defontaine ◽  
O. Kellermann ◽  
M. Paillard ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Cortical Cell ◽  
Membrane Vesicles ◽  
Cytochalasin D ◽  
The State ◽  
Protein Abundance ◽  
Transport Activity ◽  
Cortical Cells ◽  
Actin Organization ◽  
Luminal Membrane

The present study was addressed to define the contribution of cytoskeleton elements in the kidney proximal tubule Na+/H+ exchanger 3 (NHE3) activity under basal conditions. We used luminal membrane vesicles (LMV) isolated from suspensions of rat cortical tubules pretreated with either colchicine (Colch) or cytochalasin D (Cyto D). Colch pretreatment of suspensions (200 μM for 60 min) moderately decreased LMV NHE3 activity. Cyto D pretreatment (1 μM for 60 min) elicited an increase in LMV NHE3 transport activity but did not increase Na-glucose cotransport activity. Cyto D pretreatment of suspensions did not change the apparent affinity of NHE3 for internal H+. In contrast, after Cyto D pretreatment of the suspensions, NHE3 protein abundance was increased in LMV and remained unchanged in cortical cell homogenates. The effect of Cyto D on NHE3 was further assessed with cultures of murine cortical cells. The amount of surface biotinylated NHE3 increased on Cyto D treatment, whereas NHE3 protein abundance was unchanged in cell homogenates. In conclusion, under basal conditions NHE3 activity depends on the state of actin organization possibly involved in trafficking processes between luminal membrane and intracellular compartment.

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