THE EFFECT OF INSULIN ON HUMAN ADIPOSE TISSUE

1964 ◽  
Vol 42 (11) ◽  
pp. 1623-1635 ◽  
Author(s):  
A. Kahlenberg ◽  
N. Kalant
Keyword(s):  
Serum Albumin ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Utilization ◽  
Fatty Acid Content ◽  
Diabetic Patients ◽  
Fat Pad ◽  
Glucose Content ◽  
Rate Limiting ◽  
Intracellular Glucose

The effects of insulin on glucose transport and dissimilation have been studied in the rat fat pad and in human omentum. Intracellular glucose could not be demonstrated in the non-diabetic rat fat pad, with or without insulin. Slices of omentum, obtained during surgery from diabetic and non-diabetic patients, were incubated in a bicarbonate medium with a glucose concentration of 5.6 mM. Omentum from non-diabetic patients had intracellular glucose while diabetic tissue had none. Diabetic tissue had a significantly lower glucose uptake. In both, insulin stimulated glucose uptake in inverse relation to the basal uptake; but for comparable basal uptakes, the response to insulin was decreased in diabetic tissue. Glucose phosphorylation in omental tissue from non-diabetic humans had an apparent Km of 1.10 m M and a Vmax of 1.44 mg/g hour.Insulin (0.1 units/ml), bovine or human serum albumin, or a combination of insulin and bovine albumin, each increased glucose utilization by slices of non-diabetic omentum without affecting the intracellular glucose content or the free fatty acid content. In omental homogenates (cell-free), insulin and bovine serum albumin each increased the glucose utilization. In the presence of albumin, insulin increased the utilization only after the addition of glucose-6-phosphate dehydrogenase and phosphohexose isomerase in amounts sufficient to establish that hexokinase was rate-limiting for glucose utilization.It is concluded that (A) in diabetic human omentum and in normal rat fat pad, transport is rate-limiting in glucose utilization; (B) insulin and albumin each stimulate both transport and phosphorylation in human omentum; (C) in human diabetes, the glucose transport process of omentum has a decreased basal rate and a decreased responsiveness to insulin.

THE EFFECT OF INSULIN AND DIABETES ON GLUCOSE METABOLISM IN HUMAN SKIN

1966 ◽  
Vol 44 (6) ◽  
pp. 801-808 ◽  
Author(s):  
A. Kahlenberg ◽  
N. Kalant
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Human Skin ◽  
Glucose Utilization ◽  
Bicarbonate Buffer ◽  
Glucose Content ◽  
Basal Rate ◽  
In Vitro Effects ◽  
Intracellular Glucose

The in vitro effects of insulin on glucose transport and dissimilation were studied in human skin. Slices of skin obtained post-mortem were incubated in phosphate and bicarbonate media with a glucose concentration of 5.6 mM. In both buffers, insulin increased the glucose uptake in non-diabetic skin without affecting the intracellular glucose content. Similar results were obtained for diabetic skin incubated in a phosphate buffer.In bicarbonate buffer, the basal rate of glucose utilization of skin from diabetics was lower than normal; this may have been the result of a defect in the phosphofructokinase reaction. Diabetic skin also had an increased responsiveness to insulin in bicarbonate buffer.Non-diabetic skin incubated in phosphate buffer had a lower basal rate of glucose uptake and a greater responsiveness to insulin than the same tissue incubated in bicarbonate buffer.It is concluded that (a) skin from diabetic humans incubated in bicarbonate buffer had a decreased basal rate of glucose utilization and increased responsiveness to insulin; (b) insulin stimulated both glucose transport and dissimilation in diabetic and non-diabetic human skin.

scholarly journals Coupled Glucose Transport and Metabolism in Cultured Neuronal Cells: Determination of the Rate-Limiting Step

1995 ◽  
Vol 15 (5) ◽  
pp. 814-826 ◽  
Author(s):  
Richard R. Whitesell ◽  
Michael Ward ◽  
Anthony L. McCall ◽  
Daryl K. Granner ◽  
James M. May
Keyword(s):  
Glucose Transport ◽  
Glucose Utilization ◽  
Neuroblastoma Cell ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting ◽  
Intracellular Glucose

In brain and nerves the phosphorylation of glucose, rather than its transport, is generally considered the major rate-limiting step in metabolism. Since little is known regarding the kinetic coupling between these processes in neuronal tissues, we investigated the transport and phosphorylation of [2-3H]glucose in two neuronal cell models: a stable neuroblastoma cell line (NCB20), and a primary culture of isolated rat dorsal root ganglia cells. When transport and phosphorylation were measured in series, phosphorylation was the limiting step, because intracellular glucose concentrations were the same as those outside of cells, and because the apparent Km for glucose utilization was lower than expected for the transport step. However, the apparent Km was still severalfold higher than the Km of hexokinase I. When [2-3H]glucose efflux and phosphorylation were measured from the same intracellular glucose pool in a parallel assay, rates of glucose efflux were three- to-fivefold greater than rates of phosphorylation. With the parallel assay, we observed that activation of glucose utilization by the sodium channel blocker veratridine caused a selective increase in glucose phosphorylation and was without effect on glucose transport. In contrast to results with glucose, both cell types accumulated 2-deoxy-d-[14C]glucose to concentrations severalfold greater than extracellular concentrations. We conclude from these studies that glucose utilization in neuronal cells is phosphorylation-limited, and that the coupling between transport and phosphorylation depends on the type of hexose used.

Control of glucose transport in adipose tissue of the rat: Role of insulin, ATP, and intracellular metabolites

1978 ◽  
Vol 56 (7) ◽  
pp. 708-712 ◽  
Author(s):  
Mitchell L. Halperin ◽  
Marina L. Mak ◽  
Wayne M. Taylor
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Maximum Velocity ◽  
Pentose Phosphate ◽  
Maximal Velocity ◽  
Rate Limiting ◽  
Phenazine Methosulphate ◽  
Intracellular Glucose

The purpose of this study was to elucidate some of the mechanisms of control of the glucose transport step in adipose tissue. Glucose transport was studied by monitoring the conversion of [1-14C]glucose to 14CO2 in a system where glucose transport was made rate limiting by increasing the flux through the pentose phosphate pathway with phenazine methosulphate, an agent which results in rapid rates of reoxidation of NADPH. The maximum velocity for the apparent rate of glucose transport was increased significantly by insulin. There was no change in the glucose concentration required for half-maximal rates of 14CO2 production. Glucose transport was also monitored by directly measuring the rate of glucose uptake. Glucose uptake was increased by phenazine methosulphate. The intracellular glucose-6-phosphate concentration was decreased by phenazine methosulphate. These two agents, insulin and phenazine methosulphate, seemed to act by independent mechanisms as their optimal effects on glucose uptake were additive.The apparent rate of glucose transport was decreased by ATP which resulted in a decrease in maximal velocity but did not affect the affinity for glucose. This effect of ATP was seen in the presence or absence of insulin.

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.

Human GLUT-2 overexpression does not affect glucose-stimulated insulin secretion in MIN6 cells

1995 ◽  
Vol 269 (5) ◽  
pp. E897-E902
Author(s):  
H. Ishihara ◽  
T. Asano ◽  
K. Tsukuda ◽  
H. Katagiri ◽  
K. Inukai ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Utilization ◽  
Glucose Sensing ◽  
Min6 Cells ◽  
Over Expression ◽  
Twofold Increase ◽  
Glucose Stimulated Insulin Secretion ◽  
Glucose Responsiveness

Accumulated evidence suggests that GLUT-2, in addition to its role in glucose transport, may also have other functions in glucose-stimulated insulin secretion. As a first step in addressing this possibility, we have engineered MIN6 cells overexpressing human GLUT-2 by transfection with human GLUT-2 cDNA. Stable transformants harboring human GLUT-2 cDNA exhibited an approximately twofold increase in 3-O-methyl-D-glucose uptake at 0.5 and 15 mM. Glucokinase activity or glucose utilization measured by conversion of [5-3H]glucose to [3H]H2O was not, however, altered in the MIN6 cells overexpressing human GLUT-2. Furthermore, glucose-stimulated insulin secretion was not affected by over-expression of human GLUT-2. An abundance of GLUT-2, therefore, does not correlate with the glucose responsiveness of cells in which glycolysis is regulated at the glucose phosphorylating step. These data suggest that GLUT-2 by itself does not have significant functions other than its role in glucose transport in glucose sensing by MIN6 cells.

Regulation of glucose transport and GLUT-1 expression by iron chelators in muscle cells in culture

1995 ◽  
Vol 269 (6) ◽  
pp. E1052-E1058 ◽  
Author(s):  
R. Potashnik ◽  
N. Kozlovsky ◽  
S. Ben-Ezra ◽  
A. Rudich ◽  
N. Bashan
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Utilization ◽  
Fold Increase ◽  
Muscle Cells ◽  
Iron Chelator ◽  
Whole Body ◽  
Iron Chelators ◽  
Glut 1

Possible association between the degree of iron load and glucose metabolism has been postulated by both in vivo and in vitro studies. Because skeletal muscle plays a major role in whole body glucose utilization, we evaluated the effect of iron chelators deferoxamine (DFO) and bipyridyl (Bip) on glucose metabolism and transport in cultured L6 muscle cells. Bip (0.1 mM) or DFO (0.5 mM) added for 24 h to the culture medium increased glucose consumption, lactate production, and [14C]glucose incorporation into glycogen by approximately twofold. 2-Deoxy-glucose uptake by L6 myotubes increased time dependently, reaching a 5-fold and 2.5-fold increase after 12 h for Bip and DFO, respectively. Insulin induced a 2.5-fold increase in glucose uptake in untreated cells, which was additive to the chelator's effect. Iron chelator-induced glucose transport stimulation was inhibited by cycloheximide (2.5 micrograms/ml), indicating dependence on de novo protein synthesis. Increases in GLUT-1 protein and mRNA concentration, without changes in GLUT-4, were found to be responsible for iron chelator effects. We conclude that L6 cells adapt to reduction in iron availability by increasing glucose utilization through an enhanced expression of GLUT-1, without losing their physiological response to insulin.

Leg glucose uptake during maximal dynamic exercise in humans

1986 ◽  
Vol 251 (1) ◽  
pp. E65-E70 ◽  
Author(s):  
A. Katz ◽  
S. Broberg ◽  
K. Sahlin ◽  
J. Wahren
Keyword(s):  
Glucose Uptake ◽  
Glucose Utilization ◽  
Energy State ◽  
Submaximal Exercise ◽  
Dynamic Exercise ◽  
Heavy Exercise ◽  
The Mean ◽  
Muscle Biopsies ◽  
Exercise In Humans ◽  
Intracellular Glucose

Leg glucose uptake (LGU) during submaximal (50% maximal O2 uptake) and maximal dynamic exercise (97%) has been quantified from the product of the leg blood flow and the arterial minus femoral venous glucose concentration. Muscle biopsies were also obtained. During 15 min of submaximal exercise the mean LGU values ranged from 1.07 to 1.25 mmol/min, which demonstrates that LGU was stable under this condition. In contrast, during maximal exercise LGU increased continuously, reaching 2.38 +/- 0.22, 2.95 +/- 0.32, and 3.82 +/- 0.34 mmol/min after 2, 4, and 5.2 min (fatigue), respectively. The mean LGU was negatively related to the mean muscle phosphocreatine content (r = -1.00;P less than 0.01). Intracellular glucose-6-phosphate (G-6-P) and glucose were very low at rest and did not change significantly during submaximal exercise (P greater than 0.05). However, at fatigue G-6-P and glucose increased substantially and were both 8.5 mmol/kg dry muscle (P less than 0.001). These findings demonstrate that during heavy exercise glucose accumulates in the cell probably due to hexokinase inhibition by G-6-P, and thus the rate of glucose utilization appears to be lower than the rate of glucose uptake. It is suggested that 1) LGU during short-term exercise is dependent on the energy state of the muscle and 2) LGU is equal to leg glucose utilization during submaximal exercise but is in excess of utilization during heavy exercise.

Sarcolemmal glucose transport and GLUT-4 translocation during exercise are diminished by endurance training

1998 ◽  
Vol 274 (1) ◽  
pp. E89-E95 ◽  
Author(s):  
Erik A. Richter ◽  
Palle Jensen ◽  
Bente Kiens ◽  
Søren Kristiansen
Keyword(s):  
Glucose Uptake ◽  
Endurance Training ◽  
Glucose Transport ◽  
Power Output ◽  
Glucose Utilization ◽  
Work Load ◽  
Transport Capacity ◽  
Glut 4 ◽  
Glut 4 Translocation ◽  
Exercise Induced

Glucose utilization during exercise of a given submaximal power output is decreased after endurance training. The aim of the present study was to elucidate the mechanisms behind this phenomenon by utilizing the sarcolemmal giant vesicle technique. Eight healthy young untrained men endurance trained one thigh for 3 wk. They then exercised both thighs simultaneously at the same work load (77% of peak O2 uptake of the untrained thigh) for 40 min. Training increased muscle GLUT-4 protein by 70% ( P < 0.05). Glucose uptake during exercise was 38% lower ( P < 0.05) in the trained (T) thigh than in the untrained (UT) thigh because of both a lower ( P < 0.05) glucose extraction and blood flow in T. During exercise, sarcolemmal GLUT-4 protein content and glucose transport capacity increased significantly less in T than in UT muscle, and muscle glucose concentration was lower in T compared with UT ( P < 0.05) at the end of exercise. It is concluded that, despite a large increase in muscle GLUT-4 with endurance training, exercise of a given submaximal power output increases muscle glucose uptake less in T than in UT muscle. It is suggested that the mechanism behind this phenomenon is blunted exercise-induced translocation of GLUT-4 to the sarcolemma, resulting in a blunted increase in sarcolemmal glucose transport in T muscle.

Rate-limiting steps for insulin-mediated glucose uptake into perfused rat hindlimb

1986 ◽  
Vol 250 (1) ◽  
pp. E100-E102 ◽  
Author(s):  
K. Kubo ◽  
J. E. Foley
Keyword(s):  
Glucose Uptake ◽  
Glucose Transport ◽  
Transport System ◽  
Glucose Concentration ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Glucose Transport System ◽  
Glucose Clearance ◽  
Rate Limiting ◽  
Uptake And Metabolism

To determine the glucose and insulin concentrations at which glucose transport is rate limiting for insulin-mediated glucose uptake and metabolism in muscle, glucose clearance was determined in the presence of glucose concentrations ranging from trace to 20 mM and in the absence or presence of insulin in the perfused rat hindlimb. In the absence of insulin and at submaximally stimulating insulin concentrations glucose clearance was constant up to 7 mM glucose and then decreased as the glucose concentration was raised. At maximally stimulating insulin concentrations glucose clearance was constant up to 2 mM glucose and then decreased. The decrease in glucose clearance between 2 and 7 mM glucose in the presence of maximally stimulating insulin concentrations could not be accounted for by competition among glucose molecules for the glucose transport system. The results suggest that at physiological glucose concentrations in the presence of maximally stimulating insulin concentrations the rate-limiting step for insulin-mediated glucose uptake and metabolism in muscle shifts from glucose transport to some step beyond transport.

THE UPTAKE OF GLUCOSE INTO CELLS AND THE ROLE OF INSULIN IN GLUCOSE TRANSPORT

1964 ◽  
Vol 42 (6) ◽  
pp. 933-944 ◽  
Author(s):  
Margaret J. Henderson
Keyword(s):  
Cell Membrane ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Levels ◽  
Insulin Transport ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Extracellular Glucose ◽  
Rate Limiting

This presentation has been restricted to the role of insulin in glucose transport in muscle cells and deals mainly with experiments using the perfused rat heart. The several possible means for glucose transfer into cells, diffusion, pores, pinocytosis, carriers, and dimerization, have been discussed; and arguments in favor of the carrier theory, namely, specificity, kinetics, inhibition, competition, and counterflow, have been elaborated. Glucose uptake has been considered to consist of three sequential steps: (1) passage of glucose from within the capillary to the cell surface, (2) transport across the cell membrane, and (3) metabolism of glucose within the cell. The first is considered to take place by diffusion and not to be significantly limiting under normal conditions, nor to be influenced by insulin. Transport across the cell membrane is thought to be mainly under the control of insulin and is the major rate-limiting step in glucose uptake when the extracellular glucose levels are in the normal range. Metabolism of glucose within the cell is the major rate-limiting step in glucose uptake when intracellular glucose concentration is so high that its phosphorylation is near saturation.

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