Role of microvillar cell surfaces in the regulation of glucose uptake and organization of energy metabolism

2002 ◽  
Vol 282 (1) ◽  
pp. C1-C26 ◽  
Author(s):  
Klaus Lange
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Metabolic Regulation ◽  
General Concept ◽  
Characteristic Functions ◽  
Resting Cells ◽  
Cell Surfaces ◽  
Differentiated Cells ◽  
Microfilament Bundle ◽  
Metabolic Substrates

Experimental evidence suggesting a type of glucose uptake regulation prevailing in resting and differentiated cells was surveyed. This type of regulation is characterized by transport-limited glucose metabolism and depends on segregation of glucose transporters on microvilli of differentiated or resting cells. Earlier studies on glucose transport regulation and a recently presented general concept of influx regulation for ions and metabolic substrates via microvillar structures provide the basic framework for this theory. According to this concept, glucose uptake via transporters on microvilli is regulated by changes in the structural organization of the microfilament bundle, which is acting as a diffusion barrier between the microvillar tip compartment and the cytoplasm. Both microvilli formation and the switch of glucose metabolism from “metabolic regulation” to “transport limitation” occur during differentiation. The formation of microvillar cell surfaces creates the essential preconditions to establish the characteristic functions of specialized tissue cells including the coordination between glycolysis and oxidative phosphorylation, regulation of cellular functions by external signals, and Ca2+ signaling. The proposed concept integrates various aspects of glucose uptake regulation into a ubiquitous cellular mechanism involved in regulation of transmembrane ion and substrate fluxes.

scholarly journals Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Mayarling Francisca Troncoso ◽  
Mario Pavez ◽  
Carlos Wilson ◽  
Daniel Lagos ◽  
Javier Duran ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Cardiac Hypertrophy ◽  
Glucose Uptake ◽  
Male Rats ◽  
Cardiomyocyte Hypertrophy ◽  
Mrna Levels ◽  
Elevated Glucose ◽  
Amp Activated Protein Kinase ◽  
Cultured Cardiomyocytes

Abstract Background Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake—via AMP-activated protein kinase (AMPK)—after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). Methods Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). Results Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels. Conclusion These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

scholarly journals LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Monira Obaid ◽  
S. M. Nashir Udden ◽  
Prasanna Alluri ◽  
Subhrangsu S. Mandal
Keyword(s):  
Immune Response ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Immune Cells ◽  
Glucose Transporter ◽  
Energy Needs ◽  
Glut1 Expression ◽  
Lncrna Hotair ◽  
Upstream Regulators ◽  
Glucose Transporter Glut1

AbstractInflammation plays central roles in the immune response. Inflammatory response normally requires higher energy and therefore is associated with glucose metabolism. Our recent study demonstrates that lncRNA HOTAIR plays key roles in NF-kB activation, cytokine expression, and inflammation. Here, we investigated if HOTAIR plays any role in the regulation of glucose metabolism in immune cells during inflammation. Our results demonstrate that LPS-induced inflammation induces the expression of glucose transporter isoform 1 (Glut1) which controls the glucose uptake in macrophages. LPS-induced Glut1 expression is regulated via NF-kB activation. Importantly, siRNA-mediated knockdown of HOTAIR suppressed the LPS-induced expression of Glut1 suggesting key roles of HOTAIR in LPS-induced Glut1 expression in macrophage. HOTAIR induces NF-kB activation, which in turn increases Glut1 expression in response to LPS. We also found that HOTAIR regulates glucose uptake in macrophages during LPS-induced inflammation and its knockdown decreases LPS-induced increased glucose uptake. HOTAIR also regulates other upstream regulators of glucose metabolism such as PTEN and HIF1α, suggesting its multimodal functions in glucose metabolism. Overall, our study demonstrated that lncRNA HOTAIR plays key roles in LPS-induced Glut1 expression and glucose uptake by activating NF-kB and hence HOTAIR regulates metabolic programming in immune cells potentially to meet the energy needs during the immune response.

scholarly journals Low-Dose Acrolein, an Endogenous and Exogenous Toxic Molecule, Inhibits Glucose Transport via an Inhibition of Akt-Regulated GLUT4 Signaling in Skeletal Muscle Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7228
Author(s):  
Ching-Chia Wang ◽  
Huang-Jen Chen ◽  
Ding-Cheng Chan ◽  
Chen-Yuan Chiu ◽  
Shing-Hwa Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Urinary acrolein adduct levels have been reported to be increased in both habitual smokers and type-2 diabetic patients. The impairment of glucose transport in skeletal muscles is a major factor responsible for glucose uptake reduction in type-2 diabetic patients. The effect of acrolein on glucose metabolism in skeletal muscle remains unclear. Here, we investigated whether acrolein affects muscular glucose metabolism in vitro and glucose tolerance in vivo. Exposure of mice to acrolein (2.5 and 5 mg/kg/day) for 4 weeks substantially increased fasting blood glucose and impaired glucose tolerance. The glucose transporter-4 (GLUT4) protein expression was significantly decreased in soleus muscles of acrolein-treated mice. The glucose uptake was significantly decreased in differentiated C2C12 myotubes treated with a non-cytotoxic dose of acrolein (1 μM) for 24 and 72 h. Acrolein (0.5–2 μM) also significantly decreased the GLUT4 expression in myotubes. Acrolein suppressed the phosphorylation of glucose metabolic signals IRS1, Akt, mTOR, p70S6K, and GSK3α/β. Over-expression of constitutive activation of Akt reversed the inhibitory effects of acrolein on GLUT4 protein expression and glucose uptake in myotubes. These results suggest that acrolein at doses relevant to human exposure dysregulates glucose metabolism in skeletal muscle cells and impairs glucose tolerance in mice.

Glucose metabolism in resting cells ofCandida albicans as studied by13C NMR

1991 ◽  
Vol 15 (3) ◽  
pp. 279-282 ◽  
Author(s):  
Osamu Shimokawa ◽  
Keiichi Kawano ◽  
Hiroaki Nakayama
Keyword(s):  
Glucose Metabolism ◽  
Resting Cells ◽  
Ofcandida Albicans

Differential glycolytic and glycogenogenic transduction pathways in male and female bovine embryos produced in vitro

2012 ◽  
Vol 24 (2) ◽  
pp. 344 ◽  
Author(s):  
M. Garcia-Herreros ◽  
I. M. Aparicio ◽  
D. Rath ◽  
T. Fair ◽  
P. Lonergan
Keyword(s):  
Glucose Metabolism ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Bovine Embryos ◽  
High Concentration ◽  
Glucose Transporter 1 ◽  
Male And Female ◽  
Glut 1

Previous studies have shown that developmental kinetic rates following IVF are lower in female than in male blastocysts and that this may be related to differences in glucose metabolism. In addition, an inhibition of phosphatidylinositol 3-kinase (PI3-K) inhibits glucose uptake in murine blastocysts. Therefore, the aim of this study was to identify and compare the expression of proteins involved in glucose metabolism (hexokinase-I, HK-I; phosphofructokinase-1, PFK-1; pyruvate kinase1/2, PK1/2; glyceraldehyde-3-phosphate dehydrogenase, GAPDH; glucose transporter-1, GLUT-1; and glycogen synthase kinase-3, GSK-3) in male and female bovine blastocysts to determine whether PI3-K has a role in the regulation of the expression of these proteins. Hexokinase-I, PFK-1, PK1/2, GAPDH and GLUT-1 were present in bovine embryos. Protein expression of these proteins and GSK-3 was significantly higher in male compared with female blastocysts. Inhibition of PI3-K with LY294002 significantly decreased the expression of HK-I, PFK-1, GAPDH, GSK-3 A/B and GLUT-1. Results showed that the expression of glycolytic proteins HK-I, PFK-1, GAPDH and PK1/2, and the transporters GLUT-1 and GSK-3 is regulated by PI3-K in bovine blastocysts. Moreover, the differential protein expression observed between male and female blastocysts might explain the faster developmental kinetics seen in males, as the expression of main proteins involved in glycolysis and glycogenogenesis was significantly higher in male than female bovine embryos and also could explain the sensitivity of male embryos to a high concentration of glucose, as a positive correlation between GLUT-1 expression and glucose uptake in embryos has been demonstrated.

TXNIP links anticipatory unfolded protein response to estrogen reprogramming glucose metabolism in breast cancer cells

Endocrinology ◽  
2021 ◽  
Author(s):  
Yuanzhong Wang ◽  
Shiuan Chen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Unfolded Protein Response ◽  
Cancer Cells ◽  
Warburg Effect ◽  
Breast Cancer Cells ◽  
Unfolded Protein ◽  
Protein Response

Abstract Estrogen and estrogen receptor (ER) play a fundamental role in breast cancer. To adapt the rapid proliferation of ER+ breast cancer cells, estrogen increases glucose uptake and reprograms glucose metabolism. Meanwhile, estrogen/ER activates the anticipatory unfolded protein response (UPR) preparing cancer cells for the increased protein production required for subsequent cell proliferation. Here, we report that thioredoxin-interacting protein (TXNIP) is an important regulator of glucose metabolism in ER+ breast cancer cells, and estrogen/ER increases glucose uptake and reprograms glucose metabolism via activating anticipatory unfolded protein response (UPR) and subsequently repressing TXNIP expression. By using two widely used ER+ breast cancer cell lines MCF7 and T47D, we showed that MCF7 cells express high TXNIP levels and exhibit mitochondrial oxidative phosphorylation (OXPHOS) phenotype, while T47D cells express low TXNIP levels and display aerobic glycolysis (Warburg effect) phenotype. Knockdown of TXNIP promoted glucose uptake and Warburg effect, while forced overexpression of TXNIP inhibited glucose uptake and Warburg effect. We further showed that estrogen represses TXNIP expression and activates UPR sensor inositol-requiring enzyme 1 (IRE1) via ER in the breast cancer cells, and IRE1 activity is required for estrogen suppression of TXNIP expression and estrogen-induced cell proliferation. Together, our study suggests that TXNIP is involved in estrogen-induced glucose uptake and metabolic reprogramming in ER+ breast cancer cells, and links anticipatory UPR to estrogen reprogramming glucose metabolism.

Effect of calorie restriction on in vivo glucose metabolism by individual tissues in rats

1999 ◽  
Vol 276 (4) ◽  
pp. E728-E738 ◽  
Author(s):  
Thomas J. Wetter ◽  
Annie C. Gazdag ◽  
David J. Dean ◽  
Gregory D. Cartee
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Calorie Restriction ◽  
The Other ◽  
Index Formula ◽  
Tracer Technique ◽  
Ad Libitum ◽  
White Fat ◽  
Fat Pads

We evaluated the effects of 8 mo of calorie restriction [CR: 60% of ad libitum (AL) food intake] on glucose uptake by 14 tissues in unanesthetized, adult (12 mo) F344×BN rats. Glucose metabolism was assessed by the 2-[3H]deoxyglucose tracer technique at 1500 or 2100. Despite an ∼60% decline in insulinemia with CR, plasma 2-[3H]deoxyglucose clearance for CR was greater than for AL at both times. A small, CR-related decrease in glucose metabolic index ([Formula: see text]) occurred only at 1500 in the spleen and heart, and this decrease was reversed at 2100. In some tissues (cerebellum, lung, kidney, soleus, and diaphragm),[Formula: see text] was unaffected by diet, regardless of time. In the other tissues (brown fat, 3 white fat pads, epitrochlearis, plantaris, and gastrocnemius),[Formula: see text] was higher or tended to be higher for CR vs. AL at one or both times. These findings indicate that 8 mo of CR did not cause a continuous reduction in in vivo glucose uptake by any tissue studied, and, in several insulin-sensitive tissues, glucose uptake was at times greater for CR vs. AL rats.

scholarly journals Importance of the route of insulin delivery to its control of glucose metabolism

2021 ◽  
Author(s):  
Dale S. Edgerton ◽  
Mary Courtney Moore ◽  
Justin M. Gregory ◽  
Guillaume Kraft ◽  
Alan D. Cherrington
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
The Body ◽  
Whole Body ◽  
Direct Effects ◽  
Pancreatic Insulin ◽  
Hepatic Glucose

Pancreatic insulin secretion produces an insulin gradient at the liver compared to the rest of the body (approximately 3:1). This physiologic distribution is lost when insulin is injected subcutaneously, causing impaired regulation of hepatic glucose production and whole body glucose uptake, as well as arterial hyperinsulinemia. Thus, the hepatoportal insulin gradient is essential to the normal control of glucose metabolism during both fasting and feeding. Insulin can regulate hepatic glucose production and uptake through multiple mechanisms, but its direct effects on the liver are dominant under physiologic conditions. Given the complications associated with iatrogenic hyperinsulinemia in patients treated with insulin, insulin designed to preferentially target the liver may have therapeutic advantages.

scholarly journals Deuterium-depleted Water Stimulates GLUT4 Translocation in the Presence of Insulin, which Leads to Decreased Blood Glucose Concentration

2020 ◽  
Author(s):  
Miklós Molnár ◽  
Katalin Horváth ◽  
Tamás Dankó ◽  
Ildikó Somlyai ◽  
Bea Zs Kovács ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Concentration ◽  
Metabolic Regulation ◽  
Natural Waters ◽  
Blood Glucose Concentration ◽  
Serum Glucose ◽  
Diabetic Rat ◽  
Dependent Manner ◽  
Glut 4 ◽  
Deuterium Depleted Water

Abstract BackgroundDeuterium (D) is a stable isotope of hydrogen (H) with a mass number of 2. It is present in natural waters in the form of HDO, at a concentration of 16.8 mmol/L, equivalent to 150 ppm. In a phase II clinical study, deuterium depletion reduced the fasting glucose concentration and insulin resistance.MethodsIn the study, we tested the effect of subnormal D-concentration on glucose metabolism in streptozotocin (STZ)-induced diabetic rat model. Animals were randomly distributed into 9 groups to test the effect of D2O (in a range of 25-150 ppm) on glucose metabolism in diabetic animals with or without 2X1 unit/day insulin treatment. Serum glucose, -fructose amine-, -HbAIC, –insulin, and urine glucose were tested. After the 8-week treatment, membrane associated GLUT-4 from soleus muscle content was estimated by Western blot technique.ResultsOur results indicate, that deuterium depletion in the presence of insulin reduced the serum glucose, -fructose amine, and -HbAIC, level on dose dependent manner. The optimal concentration of deuterium was between 125-140 ppm. After 8-week period of deuterium depletion the highest membrane-associated GLUT-4 content was detected at 125 ppm.ConclusionsThese data suggest that deuterium depletion dose-dependently enhances insulin’s effect on GLUT-4 translocation and potentiates glucose uptake in diabetic rats, which explains the lower serum glucose, -fructose amine, and -HbAIC concentrations. Based on our experimental data, deuterium-depleted water could be used to treat patients with metabolic syndrome (MS) by increasing the insulin sensitivity. The experiment indicates that the naturally occurring deuterium has an impact on metabolic regulation.

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