scholarly journals Regulation of renal tubular glucose reabsorption by Akt2/PKBβ

2010 ◽  
Vol 298 (5) ◽  
pp. F1113-F1117 ◽  
Author(s):  
Daniela S. Kempe ◽  
Gulab Siraskar ◽  
Henning Fröhlich ◽  
Anja T. Umbach ◽  
Michael Stübs ◽  
...  

Akt/PKB is known to regulate the facilitative glucose carrier GLUT4. Nothing is known, however, of the role of Akt/PKB in the regulation of renal epithelial transport. To explore whether Akt2/PKBβ influences the Na+-coupled glucose cotransporter SGLT1, human SGLT1 was expressed in Xenopus laevis oocytes with or without Akt/PKB, and electrogenic glucose transport was determined by dual-electrode voltage clamp. The coexpression of Akt/PKB in SGLT1-expressing oocytes was followed by an increase in glucose-induced currents. To study the functional significance of Akt/PKB-sensitive renal glucose transport, further experiments were performed in gene-targeted mice lacking functional Akt2/PKBβ ( akt2−/−) and in their wild-type littermates ( akt2+/+). Plasma glucose concentration was significantly higher in akt2−/− mice than in akt2+/+ mice but was virtually identical to the plasma glucose concentration in fructose-treated akt2+/+ mice. Urinary glucose excretion was significantly higher in akt2−/− mice compared with akt2+/+ mice with or without fructose treatment. Moreover, the glucose-induced depolarization of proximal tubular cells was significantly smaller in isolated, perfused renal tubules from akt2−/− mice than in those from akt2+/+ mice. In conclusion, Akt2/PKBβ plays a role in the regulation of renal glucose transport.

1991 ◽  
Vol 80 (1) ◽  
pp. 71-76 ◽  
Author(s):  
R. C. Mühlbauer ◽  
H. Fleisch

1. The renal handling of glucose was determined in male X-linked hypophosphataemic (Hyp/Y) mice and in control littermates (+/Y) aged 4 months. Plasma glucose concentration and urinary glucose excretion were measured before and during stepwise increase in glycaemia induced by an acute infusion of glucose. The relationship between plasma glucose concentration and urinary glucose excretion was monitored per ml of glomerular filtrate in mice fed high and low phosphate diets. 2. Hyp/Y mice fed the high phosphate diet showed a significantly higher glucosuria compared with +/Y littermates. When glycaemia was increased, Hyp/Y mice developed frank glucosuria earlier than +/Y animals. In Hyp/Y mice we could not find a threshold below which virtually no glucose was excreted in the urine, whereas this was clearly visible in +/Y mice. These differences persisted in animals fed the low phosphate diet. 3. Using the acute response to the glucoregulatory hormones, glucagon and insulin, administered exogenously, we found that the regulation of plasma glucose concentration did not differ between Hyp/Y and +/Y mice. 4. The significantly lower plasma glucose concentration observed in Hyp/Y as compared with +/Y mice decreased further during fasting. 5. We conclude that the renal reabsorptive capacity for glucose is defective in Hyp/Y mice and their low plasma glucose concentration may be explained by the renal leak. Therefore the X-linked phosphataemic mouse appears not only to be characterized by a defect in renal phosphate and calcium reabsorption but also by an altered glucose reabsorption.


2006 ◽  
Vol 291 (5) ◽  
pp. R1533-R1538 ◽  
Author(s):  
Ferruh Artunc ◽  
Rexhep Rexhepaj ◽  
Harald Völkl ◽  
Florian Grahammer ◽  
Christine Remy ◽  
...  

The phosphoinositide-dependent kinase-1 (PDK-1) activates the serum- and glucocorticoid-inducible kinase and protein kinase B isoforms, which, in turn, are known to stimulate the renal and intestinal Na+-dependent glucose transporter 1. The present study has been performed to explore the role of PDK-1 in electrogenic glucose transport in small intestine and proximal renal tubules. To this end, mice expressing ∼20% of PDK-1 ( pdk1 hm) were compared with their wild-type littermates ( pdk1 wt). According to Ussing chamber experiments, electrogenic glucose transport was significantly smaller in the jejunum of pdk1 hm than of pdk1 wt mice. Similarly, proximal tubular electrogenic glucose transport in isolated, perfused renal tubule segments was decreased in pdk1 hm compared with pdk1 wt mice. Intraperitoneal injection of 3 g/kg body wt glucose resulted in a similar increase of plasma glucose concentration in pdk1 hm and in pdk1 wt mice but led to a higher increase of urinary glucose excretion in pdk1 hm mice. In conclusion, reduction of functional PDK-1 leads to impairment of electrogenic intestinal glucose absorption and renal glucose reabsorption. The experiments disclose a novel element of glucose transport regulation in kidney and small intestine.


1998 ◽  
Vol 18 (6) ◽  
pp. 632-638 ◽  
Author(s):  
William J. Powers ◽  
Joan L. Rosenbaum ◽  
Carmen S. Dence ◽  
Joanne Markham ◽  
Tom O. Videen

Few data regarding early developmental changes in cerebral (blood-to-brain) glucose transport (CTXglc) and CMRglc are available for humans. We measured CBF, CTXglc, and CMRglc with positron emission tomography at 4 to 7 days of life in six preterm human infants whose estimated gestational age was 25 to 34 weeks. The Michaelis-Menten constants Kt and Tmax were estimated from CTXglc and the calculated cerebral capillary plasma glucose concentration. Mean CMRglc was 8.8 μmol 100 g−1 min−1. The CMRglc did not correlate with plasma glucose concentration ( r = .315, P = .543), whereas CTXglc showed a significant correlation with plasma glucose concentration ( r = .836, P = .038). Estimation of the Michaelis-Menten constants from the best fit to the measured data produced values of Kt = 6.0 μmol mL−1 and Tmax = 32.6 μmol 100 g−1 min−1. These values for Kt in the developing human brain are similar to those that have been reported for the mature brain of adolescent and adult humans and adult nonhuman primates, indicating the affinity of the glucose transport protein for d-glucose is similar. However, Tmax is approximately one third to one half of the comparable values for mature brain, indicating a reduced number of available luminal transporters.


1989 ◽  
Vol 9 (3) ◽  
pp. 304-314 ◽  
Author(s):  
Kentaro Mori ◽  
Nancy Cruz ◽  
Gerald Dienel ◽  
Thomas Nelson ◽  
Louis Sokoloff

The lumped constant in the operational equation of the 2-[14C]deoxyglucose (DG) method contains the factor λ that represents the ratio of the steady-state tissue distribution spaces for [14C]DG and glucose. The lumped constant has been shown to vary with arterial plasma glucose concentration. Predictions based mainly on theoretical grounds have suggested that disproportionate changes in the distribution spaces for [14C]DG and glucose and in the value of λ are responsible for these variations in the lumped constant. The influence of arterial plasma glucose concentration on the distribution spaces for DG and glucose and on λ were, therefore, determined in the present studies by direct chemical measurements. The brain was maintained in steady states of delivery and metabolism of DG and glucose by programmed intravenous infusions of both hexoses designed to produce and maintain constant arterial concentrations. Hexose concentrations were assayed in acid extracts of arterial plasma and freeze-blown brain. Graded hyperglycemia up to 28 m M produced progressive decreases in the distribution spaces of both hexoses from their normoglycemic values (e.g., ∼ – 20% for glucose and – 50% for DG at 28 m M). In contrast, graded hypoglycemia progressively reduced the distribution space for glucose and increased the space for [14C]DG. The values for λ were comparatively stable in normoglycemic and hyperglycemic conditions but rose sharply (e.g., as much as 9–10-fold at 2 m M) in severe hypoglycemia.


2014 ◽  
Vol 6 (2) ◽  
pp. 75-78
Author(s):  
Sujaya Sham ◽  
B Poornima R Bhat ◽  
Aruna Kamath

ABSTRACT Background To compare the sensitivity and specificity of fasting plasma glucose (FPG) with that of standard glucose challenge test (GCT). Materials and methods Eighty-nine eligible pregnant women underwent GCT between 24th and 28th gestational week, followed by a diagnostic 3 hours 100 gm oral glucose tolerance test within 1 week. Out patient clinic in Father Muller Medical College Hospital, Mangalore. Data was analyzed for significance by chi-square test. Results Fasting plasma glucose concentration at a threshold value of 90 mg/dl and GCT at recommended standard threshold of 140 mg/dl yielded sensitivities of 66.7% and 100% respectively and specificities of 87.3% and 46.5% respectively. Reducing the threshold value of FPG to 80 mg/dl increased the sensitivity of test to 91.7% with specificity of 54.9% which was comparable to standard GCT, in our study. Conclusion Measuring FPG concentration using a cut-off of. 80 mg/dl is an easier, tolerable and more cost effective procedure than GCT for detecting more severe cases of GDM, i.e. the diabetes mellitus group. In resource poor settings with population belonging to average risk or high risk category, FPG at a cut-off of 90 mg/dl can be used to screen GDM. How to cite this article Sham S, Bhat BPR, Kamath A. Comparative Study of Fasting Plasma Glucose Concentration and Glucose Challenge Test for Screening Gestational Diabetes Mellitus. J South Asian Feder Obst Gynae 2014;6(2):75-78.


Metabolism ◽  
2007 ◽  
Vol 56 (11) ◽  
pp. 1576-1582 ◽  
Author(s):  
Rakesh S. Birjmohun ◽  
Radjesh J. Bisoendial ◽  
Sander I. van Leuven ◽  
Mariette Ackermans ◽  
Aelko Zwinderman ◽  
...  

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