scholarly journals The effects of underfeeding for 7 d on the thermogenic and physiological response to glucose and insulin infusion (hyperinsulinaemic euglycaemic clamp)

1990 ◽  
Vol 64 (2) ◽  
pp. 427-437 ◽  
Author(s):  
I. W. Gallen ◽  
I. A. Macdonald
Keyword(s):  
Blood Pressure ◽  
Metabolic Rate ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Insulin Infusion ◽  
Cardiovascular Responses ◽  
Glucose Disposal ◽  
Euglycaemic Clamp ◽  
Healthy Women ◽  
Hyperinsulinaemic Euglycaemic Clamp

The effect of underfeeding for 7 d (at 60 kJ/kg ideal body-weight) on the thermic and physiological responses to glucose and insulin infusions (hyperinsulinaemic euglycaemic clamp) was studied in six healthy women. Underfeeding had no significant effect on baseline metabolic rate, heart rate, forearm blood flow, diastolic blood pressure, blood intermediary metabolites, plasma insulin or catecholamines, but reduced both respiratory exchange ratio (RER; control (C) 0.86 (SE 0.02), underfed (U) 0.75 (SE 0.01)P< 0.01) and systolic blood pressure (by approximately 10 mmHg,P< 0.01). Baseline forearm glucose uptake and oxygen consumption were similar in both states. During the final 30 min of the glucose and insulin infusion, metabolic rate rose by 0.43 (SE 0.05) kJ/min in the C state, but no rise was seen in the U state (P< 0.01). Glucose disposal rate (C 47.9 (SE 1.8), U 47.3 (SE 4.1) μmol/kg per min) and storage rate (C 27.5 (SE 2.4), U 31.6 (SE 3.6) μmol/kg per min) were similar in both states, but glucose oxidation rate was reduced in the U state (C 20.5 (SE 1.7), U 15.4 (SE 0.7) μmol/kg per min;P< 0.05). RER rose to a higher value in the C state than in the U state (C 0.97 (SE 0.2), U 0.80 (SE 0.01);P< 0.01). During hyperinsulinaemia, the forearm glucose uptake and O2consumption rose in both states. No significant differences were seen in the cardiovascular responses to hyperinsulinaemia in either state. Thus underfeeding abolishes the rise in thermogenesis and reduces glucose oxidation during glucose and insulin infusions in healthy women, but does not affect the glucose disposal or storage rates or the other measured responses.

scholarly journals Acute, local infusion of angiotensin II impairs microvascular and metabolic insulin sensitivity in skeletal muscle

2018 ◽  
Vol 115 (3) ◽  
pp. 590-601 ◽  
Author(s):  
Dino Premilovac ◽  
Emily Attrill ◽  
Stephen Rattigan ◽  
Stephen M Richards ◽  
Jeonga Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Skeletal Muscle ◽  
Heart Rate ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Microvascular Blood Flow ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Skeletal Muscle Glucose Uptake

Abstract Aims Angiotensin II (AngII) is a potent vasoconstrictor implicated in both hypertension and insulin resistance. Insulin dilates the vasculature in skeletal muscle to increase microvascular blood flow and enhance glucose disposal. In the present study, we investigated whether acute AngII infusion interferes with insulin’s microvascular and metabolic actions in skeletal muscle. Methods and results Adult, male Sprague-Dawley rats received a systemic infusion of either saline, AngII, insulin (hyperinsulinaemic euglycaemic clamp), or insulin (hyperinsulinaemic euglycaemic clamp) plus AngII. A final, separate group of rats received an acute local infusion of AngII into a single hindleg during systemic insulin (hyperinsulinaemic euglycaemic clamp) infusion. In all animals’ systemic metabolic effects, central haemodynamics, femoral artery blood flow, microvascular blood flow, and skeletal muscle glucose uptake (isotopic glucose) were monitored. Systemic AngII infusion increased blood pressure, decreased heart rate, and markedly increased circulating glucose and insulin concentrations. Systemic infusion of AngII during hyperinsulinaemic euglycaemic clamp inhibited insulin-mediated suppression of hepatic glucose output and insulin-stimulated microvascular blood flow in skeletal muscle but did not alter insulin’s effects on the femoral artery or muscle glucose uptake. Local AngII infusion did not alter blood pressure, heart rate, or circulating glucose and insulin. However, local AngII inhibited insulin-stimulated microvascular blood flow, and this was accompanied by reduced skeletal muscle glucose uptake. Conclusions Acute infusion of AngII significantly alters basal haemodynamic and metabolic homeostasis in rats. Both local and systemic AngII infusion attenuated insulin’s microvascular actions in skeletal muscle, but only local AngII infusion led to reduced insulin-stimulated muscle glucose uptake. While increased local, tissue production of AngII may be a factor that couples microvascular insulin resistance and hypertension, additional studies are needed to determine the molecular mechanisms responsible for these vascular defects.

Effects of hyperinsulinaemia on the cardiovascular responses to graded hypovolaemia in normal and diabetic subjects

1988 ◽  
Vol 75 (1) ◽  
pp. 85-92 ◽  
Author(s):  
A. R. Scott ◽  
T. Bennett ◽  
I. A. MacDonald
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Cell Volume ◽  
Packed Cell Volume ◽  
Cardiovascular Responses ◽  
Normal Subjects ◽  
Normal Male ◽  
Euglycaemic Clamp ◽  
Arterial Blood ◽  
Hyperinsulinaemic Euglycaemic Clamp

1. Two experiments were carried out. The first with five normal male subjects was placebo controlled and single blind, each subject being studied on two occasions. Lower body subatmospheric pressure (LBSP) was used to assess the cardiovascular effects of graded hypovolaemia before and during either a hyperinsulinaemic, euglycaemic clamp or a placebo clamp using 0.9% (w/v) NaCl only. 2. During hyperinsulinaemia, resting systolic blood pressure rose and was accompanied by forearm vasodilatation. Forearm blood flow (FABF) and heart rate (HR) were higher at each level of LBSP during than before hyperinsulinaemia. In addition, hyperinsulinaemia was accompanied by a small increase in noradrenaline, but packed cell volume did not change. 3. In the second experiment, the effects of a hyperinsulinaemic euglycaemic clamp on the cardiovascular responses to LBSP were assessed in seven diabetic subjects with peripheral and autonomic neuropathy. 4. In contrast to the normal subjects, there was a slight fall in systolic blood pressure during the clamp but no effect was noted on HR or FABF. Mean arterial blood pressure was lower at each level of LBSP during hyperinsulinaemia compared with the pre-elamp period. Packed cell volume fell during the clamp and plasma noradrenaline rose. In one of the diabetic subjects, a precipitous fall in blood pressure occurred during hyperinsulinaemia when LBSP of 10 mmHg (1.3 kPa) was applied, this manoeuvre having been well tolerated before the clamp. 5. The mode of action of hyperinsulinaemia is not clear, but there was, however, no evidence that a fall in plasma volume had occurred.

The hyperinsulinaemic–euglycaemic glucose clamp: reproducibility and metabolic effects of prolonged insulin infusion in healthy subjects

2000 ◽  
Vol 98 (4) ◽  
pp. 367-374 ◽  
Author(s):  
Mattias SOOP ◽  
Jonas NYGREN ◽  
Kerstin BRISMAR ◽  
Anders THORELL ◽  
Olle LJUNGQVIST
Keyword(s):  
Healthy Subjects ◽  
Insulin Infusion ◽  
Gradual Increase ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Metabolic Effects ◽  
Glucose Disposal ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Glucose Clamp

To examine the reproducibility of the hyperinsulinaemic–euglycaemic clamp technique at mid-physiological hyperinsulinaemia, seven healthy subjects {age 50 (25, 59) years [median (range)], body mass index 23.1 (20.8, 25.5) kg·m-2} were investigated with three 2 h hyperinsulinaemic (60 µmol·l-1)–euglycaemic (4.5 mmol·l-1) clamps performed 48 h and 14 days apart respectively. The third clamp was prolonged to 8 h in order to examine effects on glucose disposal during prolonged clamps. The glucose infusion rates (GIRs) during the three 2 h clamps were 7.41 (4.28, 10.96), 7.26 (5.38, 11.02) and 6.63 (4.42, 10.3) mg·kg-1·min-1, with a median intra-individual coefficient of variation of 5.8 (2.6, 22) %. During the 8 h clamp a highly variable gradual increase in GIR was observed, reaching a plateau between 4 and 5 h at 32 (5, 101) % above the GIR between 1 and 2 h (P < 0.05). This increase was correlated inversely with the GIR between 1 and 2 h (r = -0.82; P < 0.05), and directly with age (r = 0.86; P < 0.05). Carbohydrate oxidation measured by indirect calorimetry was stable during the repeated 2 h clamps and the 8 h clamp. Endogenous glucose production measured by infusion of [6,6-2H2]glucose was suppressed during the 8 h clamp. The 2 h hyperinsulinaemic–euglycaemic clamp is reproducible at a mid-physiological range of hyperinsulinaemia. If prolonged, it results in a delayed increase in non-oxidative glucose disposal, which is most pronounced in subjects with low insulin sensitivity. The findings underline the importance of selecting age-matched controls in studies of insulin resistance.

scholarly journals Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 374-384 ◽  
Author(s):  
Lingling Ding ◽  
Gijs H. Goossens ◽  
Yvonne Oligschlaeger ◽  
Tom Houben ◽  
Ellen E. Blaak ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Cathepsin D ◽  
Insulin Infusion ◽  
Hepatic Insulin Sensitivity ◽  
Euglycaemic Clamp ◽  
Negatively Associated ◽  
Peripheral Insulin Sensitivity ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Tnf Α ◽  
Glucose Output

Abstract Aims/hypothesis Insulin resistance in skeletal muscle and liver plays a major role in the pathophysiology of type 2 diabetes. The hyperinsulinaemic–euglycaemic clamp is considered the gold standard for assessing peripheral and hepatic insulin sensitivity, yet it is a costly and labour-intensive procedure. Therefore, easy-to-measure, cost-effective approaches to determine insulin sensitivity are needed to enable organ-specific interventions. Recently, evidence emerged that plasma cathepsin D (CTSD) is associated with insulin sensitivity and hepatic inflammation. Here, we aimed to investigate whether plasma CTSD is associated with hepatic and/or peripheral insulin sensitivity in humans. Methods As part of two large clinical trials (one designed to investigate the effects of antibiotics, and the other to investigate polyphenol supplementation, on insulin sensitivity), 94 overweight and obese adults (BMI 25–35 kg/m2) previously underwent a two-step hyperinsulinaemic–euglycaemic clamp (using [6,6-2H2]glucose) to assess hepatic and peripheral insulin sensitivity (per cent suppression of endogenous glucose output during the low-insulin-infusion step, and the rate of glucose disappearance during high-insulin infusion [40 mU/(m2 × min)], respectively). In this secondary analysis, plasma CTSD levels, CTSD activity and plasma inflammatory cytokines were measured. Results Plasma CTSD levels were positively associated with the proinflammatory cytokines IL-8 and TNF-α (IL-8: standardised β = 0.495, p < 0.001; TNF-α: standardised β = 0.264, p = 0.012). Plasma CTSD activity was negatively associated with hepatic insulin sensitivity (standardised β = −0.206, p = 0.043), independent of age, sex, BMI and waist circumference, but it was not associated with peripheral insulin sensitivity. However, plasma IL-8 and TNF-α were not significantly correlated with hepatic insulin sensitivity. Conclusions/interpretation We demonstrate that plasma CTSD activity, but not systemic inflammation, is inversely related to hepatic insulin sensitivity, suggesting that plasma CTSD activity may be used as a non-invasive marker for hepatic insulin sensitivity in humans.

Glucose uptake and pulsatile insulin infusion: euglycaemic clamp and [33H] glucose studies in healthy subjects

1986 ◽  
Vol 113 (4) ◽  
pp. 559-563 ◽  
Author(s):  
O. Schmitz ◽  
J. Arnfred ◽  
O. Hother Nielsen ◽  
H. Beck-Nielsen ◽  
H. Ørskov
Keyword(s):  
Continuous Infusion ◽  
Glucose Uptake ◽  
Healthy Subjects ◽  
Insulin Infusion ◽  
Serum Insulin ◽  
Insulin Delivery ◽  
Metabolic Clearance ◽  
Peripheral Tissues ◽  
Euglycaemic Clamp ◽  
Insulin Levels

Abstract. To test the hypothesis that insulin has a greater effect on glucose metabolism when given as pulsatile than as continuous infusion, a 354-min euglycaemic clamp study was carried out in 8 healthy subjects. At random order soluble insulin was given intravenously either at a constant rate of 0.45 mU/kg · min or in identical amounts in pulses of 1½ to 2¼ min followed by intervals of 10½ to 9¾ min. Average serum insulin levels were similar during the two infusion protocols, but pulsatile administration induced oscillations ranging between 15 and 62 μU/ml. Glucose uptake expressed as metabolic clearance rate (MCR) for glucose was significantly increased during pulsatile insulin delivery as compared with continuous administration (270–294 min: 8.7 ± 0.7 vs 6.8 ± 0.9 ml/kg · min, P < 0.01, and 330–354 min: 8.9 ± 0.5 vs 7.4 ± 0.9 ml/kg · min, P <0.05). The superior efficacy of pulsatile insulin delivery on glucose uptake was not consistently found until after 210 min of insulin administration. In both infusion protocols, endogenous glucose production as estimated by the [3-3H]glucose infusion technique was suppressed to insignificant values. Finally, the effect of insulin on endogenous insulin secretion and lipolysis as assessed by changes in serum C-peptide and serum FFA was uninfluenced by the infusion mode. In conclusion, insulin infusion resulting in physiological serum insulin levels enhances glucose uptake in peripheral tissues in healthy subjects to a higher degree when given in a pulsed pattern mimicking that of the normal endocrine pancreas than when given as a continuous infusion.

Basal plasma insulin levels exert a qualitative but not quantitative effect on glucose-mediated glucose uptake

1995 ◽  
Vol 268 (6) ◽  
pp. E1089-E1095 ◽  
Author(s):  
S. Del Prato ◽  
A. Riccio ◽  
S. Vigili de Kreutzenberg ◽  
M. Dorella ◽  
A. Tiengo ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Critical Role ◽  
Glucose Disposal ◽  
Insulin Levels ◽  
Hyperglycemic Clamp ◽  
Basal Plasma ◽  
Plasma Insulin Levels ◽  
Total Body

We assessed the effect of hyperglycemia on glucose uptake in the presence of normal basal insulin levels or somatostatin-induced hypoinsulinemia in seven normal volunteers during a 200-min hyperglycemic clamp (+ 9 mmol/l) carried out with [3-3H]glucose and indirect calorimetry. Hyperglycemia increased glucose uptake to 22.4 +/- 2.6 and 21.3 +/- 1.6 mumol.kg-1.min-1 with and without insulin replacement, respectively. Normoinsulinemia increased glucose oxidation (delta = + 4.5 +/- 0.6 mumol.kg-1.min-1) and nonoxidative glucose metabolism (delta = + 5.2 +/- 1.7 mumol.kg-1.min-1), whereas with insulinopenia, glucose oxidation did not change (delta = -0.3 +/- 0.6 mumol.kg-1.min-1), and nonoxidative glucose metabolism increased (delta = + 48.7 +/- 0.8 mumol.kg-1.min-1). Nonoxidative glucose metabolism was higher during insulinopenic (13.5 +/- 1.8 mumol.kg-1.min-1) than normoinsulinemic hyperglycemia (9.8 +/- 2.7 mumol.kg-1.min-1; P < 0.01). Plasma FFA concentration and lipid oxidation were higher with insulinopenia. Blood lactate and alanine concentrations were greater with normoinsulinemia. In conclusion: 1) hyperglycemia promotes glucose uptake by stimulating both nonoxidative and oxidative glucose disposal; 2) the ability of hyperglycemia to enhance total body glucose uptake is similar with and without normoinsulinemia; 3) although acute insulinopenia does not impair the ability of hyperglycemia to stimulate glucose uptake, it plays a critical role in determining the intracellular metabolic fate of glucose taken up in response to hyperglycemia.

Energy expenditure and substrate metabolism in ethanol-induced liver cirrhosis

1991 ◽  
Vol 260 (3) ◽  
pp. E338-E344 ◽  
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.

Intramyocellular lipid levels are associated with peripheral, but not hepatic, insulin sensitivity in normal healthy subjects

2009 ◽  
Vol 117 (3) ◽  
pp. 111-118 ◽  
Author(s):  
Burak Salgin ◽  
Alison J. Sleigh ◽  
Rachel M. Williams ◽  
Sarah J. Jackson ◽  
Les J. Bluck ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Fat Mass ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Resonance Spectroscopy ◽  
Intramyocellular Lipid ◽  
1H Mrs ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp

Increased levels of IMCL (intramyocellular lipid) have been shown to be associated with reduced steady-state glucose infusion rates during a hyperinsulinaemic–euglycaemic clamp (M-value). The aim of the present study was to explore how IMCL levels relate to the insulin-mediated suppression of endogenous glucose production [hepatic SI (insulin sensitivity)] and increase in glucose disposal (peripheral SI). In the present study, 11 healthy young adults (7 male, 4 female; aged 21–31 years) undertook, in random order, an hyperinsulinaemic–euglycaemic clamp combined with stable glucose isotope enrichment to measure peripheral and hepatic SI, a 1H-MRS (proton-magnetic resonance spectroscopy) scan to determine IMCL levels and a DXA (dual-energy X-ray absorptiometry) scan to assess body composition. IMCL levels (range, 3.2–10.7) were associated with whole-body fat mass (r=0.787, P=0.004), fat mass corrected for height (r=0.822, P=0.002) and percentage of central fat mass (r=0.694, P=0.02), but were not related to whole-body FFM (fat-free mass; r=−0.472, P=0.1). IMCL levels correlated closely with the M-value (r=−0.727, P=0.01) and FFM-corrected peripheral SI (r=−0.675, P=0.02), but were not related to hepatic SI adjusted for body weight (r=0.08, P=0.8). The results of the present study suggest that IMCL accumulation may be a sensitive marker for attenuations in peripheral, but not hepatic, SI in normal populations. Given the close relationship of IMCL levels to whole-body and central abdominal fat mass, relative increases in the flux of lipids from adipose tissue to the intramyocellular compartment may be an integral part of the mechanisms underlying reductions in SI.

Glucose oxidation and nonoxidative glucose disposal during prolonged fasts of the northern elephant seal pup (Mirounga angustirostris)

2012 ◽  
Vol 303 (5) ◽  
pp. R562-R570 ◽  
Author(s):  
Dorian S. Houser ◽  
Daniel E. Crocker ◽  
Michael S. Tift ◽  
Cory D. Champagne
Keyword(s):  
Metabolic Rate ◽  
Glucose Oxidation ◽  
Tricarboxylic Acid Cycle ◽  
Elephant Seal ◽  
The Body ◽  
Constant Infusion ◽  
Glucose Disposal ◽  
Metabolic Demand ◽  
Northern Elephant Seal ◽  
Specific Oxidation

Elephant seal weanlings demonstrate rates of endogenous glucose production (EGP) during protracted fasts that are higher than predicted on the basis of mass and time fasting. To determine the nonoxidative and oxidative fate of endogenously synthesized glucose, substrate oxidation, metabolic rate, glycolysis, and EGP were measured in fasting weanlings. Eight weanlings were sampled at 14 days of fasting, and a separate group of nine weanlings was sampled at 49 days of fasting. Metabolic rate was determined via flow-through respirometry, and substrate-specific oxidation was determined from the respiratory quotient and urinary nitrogen measurements. The rate of glucose disposal (GluRd) was determined through a primed, constant infusion of [3-3H]glucose, and glycolysis was determined from the rate of appearance of 3H in the body water pool. GluRd was 1.41 ± 0.27 and 0.95 ± 0.21 mmol/min in the early and late fasting groups, respectively. Nearly all EGP went through glycolysis, but the percentage of GluRd oxidized to meet the daily metabolic demand was only 24.1 ± 4.4% and 16.7 ± 5.9% between the early and late fasting groups. Glucose oxidation was consistently less than 10% of the metabolic rate in both groups. This suggests that high rates of EGP do not support substrate provisions for glucose-demanding tissues. It is hypothesized that rates of EGP may be ancillary to the upregulation of the tricarboxylic acid cycle to meet high rates of lipid oxidation while mitigating ketosis.

scholarly journals Acute activation of pyruvate dehydrogenase increases glucose oxidation in muscle without changing glucose uptake

2018 ◽  
Vol 315 (2) ◽  
pp. E258-E266 ◽  
Author(s):  
Lewin Small ◽  
Amanda E. Brandon ◽  
Lake-Ee Quek ◽  
James R. Krycer ◽  
David E. James ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Pyruvate Dehydrogenase ◽  
Glucose Oxidation ◽  
Kinase Inhibitor ◽  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Acetyl Coa ◽  
Insulin Resistant

Pyruvate dehydrogenase (PDH) activity is a key component of the glucose/fatty acid cycle hypothesis for the regulation of glucose uptake and metabolism. We have investigated whether acute activation of PDH in muscle can alleviate the insulin resistance caused by feeding animals a high-fat diet (HFD). The importance of PDH activity in muscle glucose disposal under insulin-stimulated conditions was determined by infusing the PDH kinase inhibitor dichloroacetate (DCA) into HFD-fed Wistar rats during a hyperinsulinemic-euglycemic clamp. Acute DCA infusion did not alter glucose infusion rate, glucose disappearance, or hepatic glucose production but did decrease plasma lactate levels. DCA substantially increased muscle PDH activity; however, this did not improve insulin-stimulated glucose uptake in insulin-resistant muscle of HFD rats. DCA infusion increased the flux of pyruvate to acetyl-CoA and reduced glucose incorporation into glycogen and alanine in muscle. Similarly, in isolated muscle, DCA treatment increased glucose oxidation and decreased glycogen synthesis without changing glucose uptake. These results suggest that, although PDH activity controls the conversion of pyruvate to acetyl-CoA for oxidation, this has little effect on glucose uptake into muscle under insulin-stimulated conditions.

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