The effect of hyperglycemia, hyperinsulinemia, and route of glucose administration on glucose oxidation and glucose storage

1. The effects of acutely raising blood ketone body levels to those seen after 72 h of starvation were examined in 10 subjects after an overnight fast. Metabolic rate and respiratory exchange ratio were measured with indirect calorimetry before and during an insulin—glucose clamp. Arteriovenous differences were measured across forearm and subcutaneous abdominal adipose tissue. 2. In response to the clamp the respiratory exchange ratio rose from 0.82 to 0.83 during 3-hydroxybutyrate infusion and from 0.83 to 0.94 during control (saline) infusion (P < 0.001). 3. Forearm glucose uptake at the end of the clamp was 4.02 ± 0.95 (3-hydroxybutyrate infusion) and 7.09 ± 1.24 mmol min−1 100 ml−1 forearm (saline infusion). Whole body glucose uptake at the end of the clamp was 72.8 ± 7.9 (3-hydroxybutyrate infusion) and 51.0 ± 3.0 (saline infusion) mmol min−1 kg−1 body weight−1. 4. 3-Hydroxybutyrate infusion reduced the baseline abdominal venous—arterialized venous glycerol difference from 84 ± 28 to 25 ± 12 mmol/l and the non-esterified fatty acid difference from 0.60 ± 0.17 to 0.02 ± 0.09 mmol/l (P < 0.05 versus saline infusion). 5. Hyperketonaemia reduces adipose tissue lipolysis and decreases insulin-mediated forearm glucose uptake. Hyperketonaemia appears to prevent insulin-stimulated glucose oxidation, but does not reduce insulin-mediated glucose storage.

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Impairment of glucose disposal by infusion of triglycerides in humans: role of glycemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.256.6.e747 ◽

1989 ◽

Vol 256 (6) ◽

pp. E747-E752 ◽

Cited By ~ 3

Author(s):

C. P. Felley ◽

E. M. Felley ◽

G. D. van Melle ◽

P. Frascarolo ◽

E. Jequier ◽

...

Keyword(s):

Glucose Oxidation ◽

Plasma Free Fatty Acid ◽

Regulatory Mechanisms ◽

Glucose Disposal ◽

Glucose Storage ◽

Interaction Term ◽

The Difference ◽

Total Glucose

The present study was designed to assess the role of hyperglycemia (150 mg/dl) vs. euglycemia (90 mg/dl) on glucose metabolism in vivo during the infusion of a triglyceride emulsion (Intralipid). Seven young healthy volunteers were studied on four occasions using the hyperinsulinemic clamp technique, twice during euglycemia and twice during hyperglycemia, without or with Intralipid. Glucose oxidation (O) was calculated from continuous respiratory exchange measurements, and glucose storage (S) was obtained as the difference between total glucose disposal (M) and O. Two-way analysis of variance with interaction term demonstrated 1) a significant increase for M with hyperglycemia and a decrease with Intralipid; no interaction, and 2) in euglycemia, O/M and S/M occurred in one-to-one ratios; on the other hand, during 150-mg/dl hyperglycemia, the ratio dropped roughly to 1:2. Intralipid had no effect on the ratio, and no interaction could be observed. These results suggest the existence of physiological regulatory mechanisms by which 1) the rise in plasma free fatty acid inhibits both oxidative and nonoxidative glucose disposal, and 2) the rise in glycemia stimulates predominantly nonoxidative glucose disposal.

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Energy expenditure and substrate metabolism in ethanol-induced liver cirrhosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.260.3.e338 ◽

1991 ◽

Vol 260 (3) ◽

pp. E338-E344 ◽

Cited By ~ 5

Author(s):

M. J. Muller ◽

A. Fenk ◽

H. U. Lautz ◽

O. Selberg ◽

H. Canzler ◽

...

Keyword(s):

Liver Cirrhosis ◽

Energy Expenditure ◽

Metabolic Rate ◽

Oxidation Rate ◽

Infusion Rate ◽

Glucose Oxidation ◽

Insulin Infusion ◽

Resting Metabolic Rate ◽

Insulin Infusion Rate ◽

Glucose Storage

Energy expenditure and substrate metabolism were investigated in 10 patients with alcoholic liver cirrhosis (EtOH-Ci) and 10 healthy controls (C). Resting metabolic rate (RMR) varied from 1,269 to 2,467 kcal/day in C and from 1,228 to 2,098 kcal/day in EtOH-Ci. RMR was significantly related to fat-free mass (FFM) in both groups, but EtOH-Ci decreased FFM and increased RMR when expressed per kilogram FFM (+33%). Glucose intolerance, hyperinsulinemia, and a decreased C-peptide-to-insulin ratio were observed in EtOH-Ci after a test meal. Concomitantly, nonoxidative glucose metabolism was reduced in association with normal increases in glucose oxidation. EtOH-Ci reduced insulin sensitivity (-59%) and maximal insulin-dependent glucose disposal (-40%) during a sequential two-step glucose clamp protocol (phase 1: 1 mU.kg body wt-1.min-1 insulin infusion rate + euglycemia; phase 2: 4 mU.kg body wt-1.min-1 insulin infusion rate + 165 mg/dl plasma glucose concentration). This was explained by reduced glucose storage (-99%, -51%) in association with normal responses in glucose oxidation rate, plasma lactate concentration, lipid oxidation rate, and rate of lipogenesis. Defective glucose storage was independent of reduced FFM. EtOH-Ci increased glucose-induced thermogenesis by 57%. We conclude that increased resting metabolic rate, enhanced thermogenesis, defective glucose storage, and normal glucose oxidation together result in increased energy needs and favor negative energy balance in patients with alcoholic cirrhosis.

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Differential regulation of intracellular glucose metabolism by glucose and insulin in human muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.265.6.e898 ◽

1993 ◽

Vol 265 (6) ◽

pp. E898-E905 ◽

Cited By ~ 8

Author(s):

L. J. Mandarino ◽

A. Consoli ◽

A. Jain ◽

D. E. Kelley

Keyword(s):

Glucose Uptake ◽

Glucose Oxidation ◽

Glycogen Synthase ◽

Human Subjects ◽

Pyruvate Dehydrogenase Complex ◽

Glycogen Synthesis ◽

Human Muscle ◽

Additional Increase ◽

Intracellular Effect ◽

Glucose Storage

Insulin and glucose stimulate glucose uptake in human muscle by different mechanisms. Insulin has well-known effects on glucose transport, glycogen synthesis, and glucose oxidation, but the effects of hyperglycemia on the intracellular routing of glucose are less well characterized. We used euglycemic and hyperglycemic clamps with leg balance measurements to determine how hyperglycemia affects skeletal muscle glucose storage, glycolysis, and glucose oxidation in normal human subjects. Glycogen synthase (GS) and pyruvate dehydrogenase complex (PDHC) activities were determined using muscle biopsies. During basal insulin replacement, hyperglycemia (11.6 +/- 0.31 mM) increased leg muscle glucose uptake (0.522 +/- 0.129 vs. 0.261 +/- 0.071 mumol.min-1 x 100 ml leg tissue-1, P < 0.05), storage (0.159 +/- 0.082 vs. -0.061 +/- 0.055, P < 0.05), and oxidation (0.409 +/- 0.080 vs. 0.243 +/- 0.085, P < 0.05) compared with euglycemia (6.63 +/- 0.33 mM). The increase in basal glucose oxidation due to hyperglycemia was associated with increased muscle PDHC activity (0.499 +/- 0.087 vs. 0.276 +/- 0.049, P < 0.05). However, the increase in leg glucose storage was not accompanied by an increase in muscle GS activity. During hyperinsulinemia, hyperglycemia (11.9 +/- 0.49 mM) also caused an additional increase in leg glucose uptake over euglycemia (6.14 +/- 0.42 mM) alone (5.75 +/- 1.25 vs. 3.75 +/- 0.58 mumol.min-1 x 100 ml leg-1, P < 0.05). In this case the major intracellular effect of hyperglycemia was to increase glucose storage (5.03 +/- 1.16 vs. 2.39 +/- 0.37, P < 0.05). At hyperinsulinemia, hyperglycemia had no effect on muscle GS or PDHC activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effects of a Single Exercise Bout on Insulin Sensitivity in Black and White Individuals

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-0019 ◽

2010 ◽

Vol 95 (10) ◽

pp. E219-E223 ◽

Cited By ~ 9

Author(s):

Rebecca E. Hasson ◽

Kirsten Granados ◽

Stuart Chipkin ◽

Patty S. Freedson ◽

Barry Braun

Keyword(s):

Body Mass Index ◽

Insulin Sensitivity ◽

Racial Differences ◽

Body Mass ◽

Glucose Oxidation ◽

Exercise Bout ◽

Whole Body ◽

Glucose Disposal ◽

Maximal Heart Rate ◽

Glucose Storage

Background: Previous research suggests non-Hispanic blacks (blacks) are more insulin resistant than non-Hispanic whites (whites). Physical activity can play an important role in reducing insulin resistance. However, it is unknown whether racial differences exist in response to exercise. Therefore, the purpose of this study was to compare metabolic responses to a single bout of exercise in blacks and age-, sex-, and body mass index-matched whites. Methods: Whole-body insulin sensitivity, glucose storage, glucose oxidation, and respiratory exchange ratio (RER) were assessed during a hyperinsulinemic-euglycemic clamp in normoglycemic blacks (n = 11) and whites (n = 10). Outcome measures were evaluated in a sedentary control condition and 12 h after treadmill walking at 75% of maximal heart rate for 75 min. Results: In the control condition, there were no differences in insulin sensitivity between blacks and whites (P = 0.54). During the clamp, glucose oxidation and insulin-stimulated RER values were significantly higher in blacks compared with whites (P = 0.04 and P < 0.01, respectively). Despite similar RER values during exercise, RER values at 60, 90, and 120 min after exercise in blacks were also significantly higher compared with whites (P < 0.05). After exercise, there were no significant improvements in insulin sensitivity (P = 0.57) or glucose storage (P = 0.42) in blacks or whites; however, glucose oxidation was significantly lower in both racial groups (P < 0.05). Conclusions: These data suggest that insulin sensitivity is similar in blacks and age-, sex-, and body mass index-matched whites, but the glucose disposal pathways (storage vs. oxidation) are somewhat different. Compared with whites, blacks appear to have a greater capacity to increase glucose oxidation immediately after exercise and during insulin stimulation.

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The Effect of Graded Doses of Insulin on Total Glucose Uptake, Glucose Oxidation, and Glucose Storage in Man

Diabetes ◽

10.2337/diacare.31.11.957 ◽

1982 ◽

Vol 31 (11) ◽

pp. 957-963 ◽

Cited By ~ 270

Author(s):

D. Thiebaud ◽

E. Jacot ◽

R. A. Defronzo ◽

E. Maeder ◽

E. Jequier ◽

...

Keyword(s):

Glucose Uptake ◽

Glucose Oxidation ◽

Glucose Storage ◽

Total Glucose

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Metabolic handling of intraduodenal vs. intravenous glucose in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.281.2.e261 ◽

2001 ◽

Vol 281 (2) ◽

pp. E261-E268 ◽

Cited By ~ 8

Author(s):

F. Féry ◽

J. Devière ◽

E. O. Balasse

Keyword(s):

Whole Body ◽

Total Carbohydrate ◽

Intravenous Glucose ◽

Glucose Administration ◽

Glucose Levels ◽

Hepatic Glucose ◽

Glucose Storage ◽

Lag Period ◽

Series Of Experiments ◽

And Storage

To determine whether the route of glucose administration affects whole body glucose metabolism, 14 healthy volunteers were randomly infused with intraduodenal (id) or intravenous (iv) glucose at 6 mg · kg−1 · min−1 for 180 min. Infused glucose was labeled with [2-3H]glucose in a first series of paired experiments designed to characterize kinetic parameters to be used in a second series of experiments in which [3-3H]- and [U-14C]glucose labeling was used to characterize the metabolic fate of infused glucose. Experiments with [2-3H]glucose showed that, after a lag period of only 20 min, id absorption averaged 105 ± 3% of infusion. During the final hour of id and iv infusion of [3-3H]glucose, tissue uptake averaged 98 ± 3 and 107 ± 4% of infusion, respectively, and was equally divided between glycolysis (3H2O production) and storage (uptake-glycolysis). Glucose oxidation (14CO2), total carbohydrate oxidation (indirect calorimetry), and net carbohydrate balance were also similar, but the thermic effect of glucose was significantly greater after id infusion. Because insulin and estimated portal vein glucose levels were similar during the final 80 min of both infusions, our results suggest that hepatic glucose storage (and therefore muscle storage estimated as whole body minus liver storage) is not affected by the route of glucose administration.

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