scholarly journals Computational Modelling of Glucose Uptake by SGLT1 and Apical GLUT2 in the Enterocyte

2021 ◽  
Vol 12 ◽  
Author(s):  
Nima Afshar ◽  
Soroush Safaei ◽  
David P. Nickerson ◽  
Peter J. Hunter ◽  
Vinod Suresh
Keyword(s):  
Blood Flow ◽  
Glucose Uptake ◽  
Glucose Concentration ◽  
Glucose Transporter ◽  
Blood Glucose Concentration ◽  
Computational Modelling ◽  
Glucose Absorption ◽  
Osmotic Gradient ◽  
Volume Changes ◽  
Blood Concentrations

It has been suggested that glucose absorption in the small intestine depends on both constitutively expressed SGLT1 and translocated GLUT2 in the brush border membrane, especially in the presence of high levels of luminal glucose. Here, we present a computational model of non-isotonic glucose uptake by small intestinal epithelial cells. The model incorporates apical uptake via SGLT1 and GLUT2, basolateral efflux into the blood via GLUT2, and cellular volume changes in response to non-isotonic conditions. The dependence of glucose absorption on luminal glucose, blood flow rate, and inlet blood glucose concentration is studied. Uptake via apical GLUT2 is found to be sensitive to all these factors. Under a range of conditions, the maximum apical GLUT2 flux is about half of the SGLT1 flux and is achieved at high luminal glucose (> 50 mM), high blood flow rates, and low inlet blood concentrations. In contrast, SGLT1 flux is less sensitive to these factors. When luminal glucose concentration is less than 10 mM, apical GLUT2 serves as an efflux pathway for glucose to move from the blood to the lumen. The model results indicate that translocation of GLUT2 from the basolateral to the apical membrane increases glucose uptake into the cell; however, the reduction of efflux capacity results in a decrease in net absorption. Recruitment of GLUT2 from a cytosolic pool elicits a 10–20% increase in absorption for luminal glucose levels in the a 20–100 mM range. Increased SGLT1 activity also leads to a roughly 20% increase in absorption. A concomitant increase in blood supply results in a larger increase in absorption. Increases in apical glucose transporter activity help to minimise cell volume changes by reducing the osmotic gradient between the cell and the lumen.

PAF increases hepatic vascular resistance and glycogenolysis in vivo

1991 ◽  
Vol 260 (3) ◽  
pp. G471-G480 ◽  
Author(s):  
K. L. Hines ◽  
A. Braillon ◽  
R. A. Fisher
Keyword(s):  
Blood Flow ◽  
Blood Glucose ◽  
Glucose Concentration ◽  
Glycogen Phosphorylase ◽  
Blood Glucose Concentration ◽  
Portal Pressure ◽  
Hepatic Glycogen ◽  
Hepatic Portal ◽  
Adrenalectomized Rats

Administration of platelet-activating factor (PAF) to portal venous circulation of anesthetized fed rats produced decreases in mean arterial pressure and increases in hepatic portal pressure and blood glucose concentration. These responses to PAF were dose dependent with ED50 values of 0.02-0.05 micrograms/kg and specific as lyso- and enantio-PAF did not reproduce effects of PAF. Specific PAF receptor antagonist SRI 63-675 (75 micrograms/kg) inhibited significantly these PAF (0.1 micrograms/kg)-induced responses in rats. Administration of prazosin (500 micrograms/kg) and propranolol (400 micrograms/kg) to rats abolished phenylephrine (50 micrograms/kg)-induced increases in mean arterial pressure, hepatic portal pressure, and blood glucose concentration but did not prevent PAF (1 microgram/kg)-induced alterations in these parameters. Glycogen phosphorylase alpha levels were increased significantly in livers of rats after administration of PAF (1 microgram/kg) or phenylephrine (50 micrograms/kg). Administration of prazosin and propranolol to rats inhibited phenylephrine- but not PAF-induced activation of hepatic glycogen phosphorylase. Hepatic adenosine 3',5'-cyclic monophosphate (cAMP) concentration was increased slightly by PAF, but these increases were eliminated by adrenergic blockade, suggesting that activation of hepatic glycogen phosphorylase by PAF is not dependent on increases in cAMP. Increases in hepatic portal pressure and blood glucose concentration in response to PAF (0.1 micrograms/kg) were not attenuated in adrenalectomized rats. Moreover, PAF (0.1 micrograms/kg) stimulated increases in hepatic portal pressure after administration of the ganglionic blocking agent chlorisondamine (2.5 mg/kg) to adrenalectomized rats. Administration of PAF (0.05 micrograms/kg) to rats instrumented with pulse Doppler flow probes produced decreases in hepatic arterial and portal vein blood flow and increases in hepatic arterial and portal vascular resistance. These observations provide direct evidence that PAF regulates hepatic hemodynamics and glycogenolysis in vivo. It is suggested that PAF plays an important role in regulating hepatic blood flow and supplying extrahepatic tissues with energy substrates by sympathetic-independent mechanism(s) after its release in acute pathophysiological situations.

scholarly journals Ecklonia cavaInhibits Glucose Absorption and Stimulates Insulin Secretion in Streptozotocin-Induced Diabetic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hye Kyung Kim
Keyword(s):  
Insulin Secretion ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Islet Cells ◽  
Glucose Absorption ◽  
Oral Glucose ◽  
Diabetic Mice ◽  
Glucose Transporter 1

Aims of study. Present study investigated the effect ofEcklonia cava(EC) on intestinal glucose uptake and insulin secretion.Materials and methods. Intestinal Na+-dependent glucose uptake (SGU) and Na+-dependent glucose transporter 1 (SGLT1) protein expression was determined using brush border membrane vesicles (BBMVs). Glucose-induced insulin secretion was examined in pancreatic β-islet cells. The antihyperglycemic effects of EC, SGU, and SGLT1 expression were determined in streptozotocin (STZ)-induced diabetic mice.Results. Methanol extract of EC markedly inhibited intestinal SGU of BBMV with the IC50value of 345 μg/mL. SGLT1 protein expression was dose dependently down regulated with EC treatment. Furthermore, insulinotrophic effect of EC extract was observed at high glucose media in isolated pancreatic β-islet cellsin vitro. We next conducted the antihyperglycemic effect of EC in STZ-diabetic mice. EC supplementation markedly suppressed SGU and SGLT1 abundance in BBMV from STZ mice. Furthermore, plasma insulin level was increased by EC treatment in diabetic mice. As a result, EC supplementation improved postprandial glucose regulation, assessed by oral glucose tolerance test, in diabetic mice.Conclusion. These results suggest that EC play a role in controlling dietary glucose absorption at the intestine and insulinotrophic action at the pancreas contributing blood glucose homeostasis in diabetic condition.

scholarly journals Computational Modelling of Glucose Uptake in the Enterocyte

Physiome ◽  
2022 ◽  
Author(s):  
Nima Afshar ◽  
Soroush Safaei ◽  
David Nickerson ◽  
Peter J. Hunter ◽  
Vinod Suresh
Keyword(s):  
Experimental Data ◽  
Glucose Transporter ◽  
Computational Modelling ◽  
Glucose Absorption ◽  
Composite Model ◽  
The Other ◽  
Sodium Glucose Cotransporter ◽  
Protein Models

We describe an implemented model of glucose absorption in the enterocyte, as previously published by Afshar et al. (2019), The model used mechanistic descriptions of all the responsible transporters and was built in the CellML framework. It was validated against published experimental data and implemented in a modular structure which allows each individual transporter to be edited independently from the other transport protein models. The composite model was then used to study the role of the sodium-glucose cotransporter (SGLT1) and the glucose transporter type 2 (GLUT2), along with the requirement for the existence of the apical Glut2 transporter, especially in the presence of high luminal glucose loads, in order to enhance the absorption. Here we demonstrate the reproduction of the figures in the original paper by using the associated model. EDITOR'S NOTE (v3): Instructions within the manuscript changed, in order to properly execute the model files. Spelling of author's name corrected in filenames. (v4): Abstract fixes.

scholarly journals Computational Modelling of Glucose Uptake in the Enterocyte

2020 ◽  
Author(s):  
Nima Afshar ◽  
Soroush Safaei ◽  
David Nickerson ◽  
Peter J. Hunter ◽  
Vinod Suresh
Keyword(s):  
Experimental Data ◽  
Glucose Transporter ◽  
Computational Modelling ◽  
Glucose Absorption ◽  
Composite Model ◽  
The Other ◽  
Sodium Glucose Cotransporter ◽  
Protein Models

We describe an implemented model of glucose absorption in the enterocyte, as previously published by Afshar et al. Afshar et al. (2019), The model used mechanistic descriptions of all the responsible transporters and was built in the CellML framework. It was validated against published experimental data and implemented in a modular structure which allows each individual transporter to be edited independently from the other transport protein models. The composite model was then used to study the role of the sodium-glucose cotransporter (SGLT1) and the glucose transporter type 2 (GLUT2), along with the requirement for the existence of the apical Glut2 transporter, especially in the presence of high luminal glucose loads, in order to enhance the absorption. Here we demonstrate the reproduction of the figures in the original paper by using the associated model.

P1131STEADY CONCENTRATION PERITONEAL DIALYSIS INCREASES ULTRAFILTRATION AND SODIUM REMOVAL COMPARED TO CAPD

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ola Carlsson ◽  
Ann-Cathrine Johansson ◽  
Olof Heimbürger ◽  
Giedre Martus ◽  
Martin Wilkie ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Concentration ◽  
Small Volume ◽  
Glucose Absorption ◽  
Control Data ◽  
Peritoneal Equilibration Test ◽  
Fluid Removal ◽  
Sodium Removal ◽  
Sodium Sieving ◽  
One Way Anova

Abstract Background and Aims Fluid and sodium removal may be a challenge during glucose-based PD, leading to increased use of high glucose solutions to maintain sufficient fluid removal. This may in turn lead to increased sodium sieving, resulting in a decreased sodium removal. Carry Life® UF uses Steady Concentration PD (SCPD), where the infusion of glucose compensates for glucose uptake and maintains the intraperitoneal glucose concentration at a sufficient level providing a continuous ultrafiltration throughout the dwell. The present study investigated the effect of Carry Life UF compared to a standard CAPD dwell regarding ultrafiltration, sodium removal and glucose absorption. Method Eight stable PD patients were included in the study. Subjects were treated with 5-hour Carry Life UF treatments using three different glucose doses (11, 14, 20 g/h). An initial fill with 1500 ml, 13.6 g/l glucose PD solution was used. A small volume of dialysate was drained hourly to avoid overfill. A standard 4-hour Peritoneal Equilibration Test (PET) (2000 ml, 22.7 g/l glucose) was used as control. Data expressed as mean ± SD, statistical analysis using one-way ANOVA. Results Ultrafiltration was significantly increased during the Carry Life UF treatments compared to PET (646±256, 739±312, 863±380 ml for 11 g/h, 14 g/h and 20 g/h, respectively, vs. 162±242 ml for PET, p<0.01). Sodium removal increased significantly during Carry Life UF treatments (86±27, 92±33, 110±37 mmol/dwell for 11, 14, and 20 g glucose/h) compared to PET (22±33 mmol/dwell, p<0.001). Figure a shows that the intraperitoneal glucose concentration increased during the first hours of the Carry Life UF treatments and remained stable during the remainder of the treatments. During PET the glucose concentration decreased gradually during the treatment. The maximum intraperitoneal glucose concentration did not exceed 26 g/l (144 mmol/l) during the Carry Life UF treatments. The UF volume per gram of glucose uptake was significantly higher for the two lower Carry Life UF glucose doses compared to PET (Figure b). Conclusion SCPD performed with Carry Life® UF maintained a stable intraperitoneal glucose concentration during the 5-hour treatment which generated significantly higher UF volumes compared to 4-hour PET. During the Carry Life UF treatments glucose was used more efficiently, particularly for the two lowest doses, in comparison to PET. The increased sodium removal with Carry Life® UF enables a better balance between UF volume and sodium removal than for example during APD. In summary, SCPD using Carry Life® UF increases the efficiency of PD compared to standard, glucose-based CAPD with respect to ultrafiltration and sodium removal.

Glucose flux from dietary disaccharides: all sugars are not absorbed at equal rates

1991 ◽  
Vol 261 (5) ◽  
pp. G818-G822 ◽  
Author(s):  
L. A. Heitlinger ◽  
B. U. Li ◽  
R. D. Murray ◽  
H. J. McClung ◽  
H. R. Sloan ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Short Circuit ◽  
Hydrolytic Enzyme ◽  
Short Circuit Current ◽  
Glucose Absorption ◽  
Glucose Flux ◽  
Free Glucose ◽  
Hydrolysis Of

Considerable discrepancies exist in the literature regarding the rates of glucose absorption from the common dietary disaccharides, lactose, maltose, and sucrose. This study compared the unidirectional flux of glucose derived from dietary disaccharides with that of their constituent monosaccharides in vitro. Lactose-stimulated short-circuit current (Isc) and mucosal-to-serosal flux (Jm----s) were lower than that of an equimolar glucose-galactose mixture and were phlorizin inhibitable. Maltose- and glucose-stimulated Isc were similar, but Jm----s of glucose derived from the hydrolysis of maltose was lower than that of free glucose. Sucrose-stimulated Isc and Jm----s were similar to that of an equimolar glucose-fructose mixture. Isc and Jm----s of glucose from both maltose and sucrose were phlorizin and acarbose inhibitable. We conclude that the rate of glucose uptake from disaccharides is less than or equal to that of free glucose and is dependent on the glucose source. We speculate that regulation of glucose uptake from disaccharides can occur at three sites: the hydrolytic enzyme, the glucose transporter, and the tight junctions.

Variation of Absorption Coefficient of Glucose Water in Consideration of Water Displacement

2010 ◽  
Vol 159 ◽  
pp. 358-362 ◽  
Author(s):  
Zhong Hai He ◽  
Guang Shuai Zhu
Keyword(s):  
Absorption Coefficient ◽  
Water Absorption ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Glucose Absorption ◽  
The Other ◽  
Total Absorption ◽  
Water Displacement ◽  
Water Absorption Coefficient ◽  
Glucose Water

Adding glucose in water will cause two influences on the aqueous solution: one is absorption coefficient addition of glucose; the other is absorption coefficient decrease of water because of water displacement. So the total absorption effect is the result of the absorption coefficient increase of glucose and absorption coefficient decrease of water. In this paper the absorption coefficient of glucose water is analyzed in consideration of water displacement. By data of handbook, we deduce a relationship between the glucose absorption coefficient addition and water absorption coefficient decrease. When one molar glucose is added into water, 6.15 molars water molecular is displaced. The wavelength selection in glucose detection should be at the place where the combined absorption is maximum. The wavelength of widely used in blood glucose concentration detection, e.g. 1.6μm, is selected as an example for analysis. When glucose is added into water, the linear relationship between glucose concentration and absorption coefficient is hold on. On the other hand, when the water molecular is decreased, the water absorption coefficient will decreased, too, which will decrease the total absorption coefficient compared to the situation without water displacement. In general, water displacement will decrease the sensitivity of absorption coefficient to glucose concentration.

Intraportal glucose infusion and pancreatic islet blood flow in anesthetized rats

2000 ◽  
Vol 279 (4) ◽  
pp. R1224-R1229 ◽  
Author(s):  
Per-Ola Carlsson ◽  
Masanori Iwase ◽  
Leif Jansson
Keyword(s):  
Blood Flow ◽  
Blood Glucose ◽  
Portal Vein ◽  
Insulin Release ◽  
Pancreatic Islet ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Islet Blood Flow ◽  
Blood Flow Increase ◽  
Selective Increase

The aim of the study was to evaluate whether a selective increase in portal vein blood glucose concentration can affect pancreatic islet blood flow. Anesthetized rats were infused (0.1 ml/min for 3 min) directly into the portal vein with saline, glucose, or 3- O-methylglucose. The infused dose of glucose (1 mg · kg body wt−1 · min−1) was chosen so that the systemic blood glucose concentration was unaffected. Intraportal infusion of d-glucose increased insulin release and islet blood flow; the osmotic control substance 3- O-methylglucose had no such effect. A bilateral vagotomy performed 20 min before the infusions potentiated the islet blood flow response and also induced an increase in whole pancreatic blood flow, whereas the insulin response was abolished. Administration of atropine to vagotomized animals did not change the blood flow responses to intraportal glucose infusions. When the vagotomy was combined with a denervation of the hepatic artery, there was no stimulation of islet blood flow or insulin release after intraportal glucose infusion. We conclude that a selective increase in portal vein blood glucose concentration may participate in the islet blood flow increase in response to hyperglycemia. This effect is probably mediated via periarterial nerves and not through the vagus nerve. Furthermore, this blood flow increase can be dissociated from changes in insulin release.

scholarly journals Regulation of Cerebral Glucose Metabolism in Normal and Polycythemic Newborn Lambs

1992 ◽  
Vol 12 (5) ◽  
pp. 856-865 ◽  
Author(s):  
Ted S. Rosenkrantz ◽  
Anthony F. Philipps ◽  
Isabella Knox ◽  
Edwin L. Zalneraitis ◽  
Patricia J. Porte ◽  
...  
Keyword(s):  
Blood Flow ◽  
Glucose Metabolism ◽  
Oxygen Uptake ◽  
Glucose Uptake ◽  
Glucose Concentration ◽  
Cerebral Glucose Metabolism ◽  
Control Group ◽  
Cerebral Oxygen ◽  
Independent Effects ◽  
Arterial Glucose

In contrast to previous investigations, a recent study of polycythemic lambs suggested that cerebral glucose delivery (concentration × blood flow), not arterial glucose concentration, determined cerebral glucose uptake. In the present study, the independent effects of arterial glucose concentration and delivery on cerebral glucose uptake were examined in two groups of chronically catheterized newborn lambs (control and polycythemic). Arterial glucose concentration was varied by an infusion of insulin. CBF was reduced in one group of lambs (polycythemic) by increasing the hematocrit. At all arterial glucose concentrations, the cerebral glucose delivery of the polycythemic group was 59.6% of the control group. At arterial glucose concentrations of > 1.6 mmol/L, cerebral glucose uptake was constant and similar in both groups. At arterial glucose concentrations of ≤1.6 mmol/L, cerebral glucose uptake was unchanged in the control group, but was significantly decreased in the polycythemic group. In contrast, the cerebral glucose uptake was similar in both groups over a broad range of cerebral glucose delivery values. At cerebral glucose delivery values ≤83 μmol/min/100 g, there was a significant decrease in cerebral glucose uptake in both groups. During periods of low cerebral glucose delivery and uptake, cerebral oxygen uptake fell in the control group but remained unchanged in the polycythemic group. Maintenance of cerebral oxygen uptake in the polycythemic group was associated with an increased extraction and uptake of lactate and β-hydroxybutyrate. We conclude that cerebral glucose delivery, not arterial glucose concentration alone, determines cerebral glucose uptake.

Measurement of interstitial muscle glucose and lactate concentrations during an oral glucose tolerance test

1996 ◽  
Vol 271 (6) ◽  
pp. E1003-E1007 ◽  
Author(s):  
M. Muller ◽  
A. Holmang ◽  
O. K. Andersson ◽  
H. G. Eichler ◽  
P. Lonnroth
Keyword(s):  
Blood Flow ◽  
Glucose Uptake ◽  
Flow Rate ◽  
Glucose Concentration ◽  
Interstitial Fluid ◽  
Human Subjects ◽  
Muscle Blood Flow ◽  
Blood Flow Rate ◽  
Capillary Wall ◽  
Oral Glucose

To study the relationship between blood flow rate and muscle metabolism, muscle microdialysis was performed in nine human subjects (5 females and 4 males) after an oral glucose load (75 g). Two microdialysis probes were inserted into the medial femoral muscle for estimation of glucose and lactate concentrations in the interstitial fluid, and the muscle blood flow was measured concomitantly with strain-gauge plethysmography. After subjects fasted overnight, their glucose concentration in arterial plasma and interstitial fluid was 4.6 +/- 0.13 vs. 3.8 +/- 0.23 mmol/l (P < 0.05), and the corresponding lactate concentrations were 0.60 +/- 0.07 vs. 0.83 +/- 0.07 mmol/l (P < 0.05). Muscle blood flow was 5.2 +/- 0.7 and 7.5 +/- 1.4 ml.100 g-1.min-1 (P < 0.05) at 0 and 90 min after oral glucose, respectively. The arterial-interstitial concentration differences of glucose increased after oral glucose [at 0 min 0.73 +/- 0.24 vs. 2.19 +/- 0.60 mmol/l at 90 min (P < 0.001)]. The corresponding values for lactate were -0.23 +/- 0.10 at 0 min vs.-0.26 +/- 0.18 mmol/l at 90 min (not significant). The data show that 1) the capillary wall is partly rate limiting for glucose uptake, and 2) after oral glucose, the glucose concentration gradient over the capillary wall increases despite a limited increase in blood flow rate, which then mediates approximately 10-20% of total enhancement of glucose uptake in muscle.

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