scholarly journals The muscle anabolic effect of protein ingestion during a hyperinsulinaemic euglycaemic clamp in middle-aged women is not caused by leucine alone

2018 ◽  
Vol 596 (19) ◽  
pp. 4681-4692 ◽  
Author(s):  
Stephan van Vliet ◽  
Gordon I. Smith ◽  
Lane Porter ◽  
Raja Ramaswamy ◽  
Dominic N. Reeds ◽  
...  
2018 ◽  
Vol 115 (3) ◽  
pp. 590-601 ◽  
Author(s):  
Dino Premilovac ◽  
Emily Attrill ◽  
Stephen Rattigan ◽  
Stephen M Richards ◽  
Jeonga Kim ◽  
...  

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.


2020 ◽  
Vol 47 (4) ◽  
pp. 725-737 ◽  
Author(s):  
Katherine M. Roberts‐Thomson ◽  
Andrew C. Betik ◽  
Dino Premilovac ◽  
Stephen Rattigan ◽  
Stephen M. Richards ◽  
...  

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 374-384 ◽  
Author(s):  
Lingling Ding ◽  
Gijs H. Goossens ◽  
Yvonne Oligschlaeger ◽  
Tom Houben ◽  
Ellen E. Blaak ◽  
...  

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.


1988 ◽  
Vol 75 (1) ◽  
pp. 85-92 ◽  
Author(s):  
A. R. Scott ◽  
T. Bennett ◽  
I. A. MacDonald

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.


1990 ◽  
Vol 64 (2) ◽  
pp. 427-437 ◽  
Author(s):  
I. W. Gallen ◽  
I. A. Macdonald

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.


2019 ◽  
Vol 33 (6) ◽  
pp. 7009-7017 ◽  
Author(s):  
William J. Smiles ◽  
Tyler A. Churchward-Venne ◽  
Luc J. C. Loon ◽  
John A. Hawley ◽  
Donny M. Camera

2018 ◽  
Vol 104 (4) ◽  
pp. 994-1004 ◽  
Author(s):  
Astrid M H Horstman ◽  
Imre W K Kouw ◽  
Jan-Willem van Dijk ◽  
Henrike M Hamer ◽  
Bart B L Groen ◽  
...  

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