Metabolic effects of dobutamine in normal man

1992 ◽  
Vol 82 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Ceri J. Green ◽  
R. S. Frazer ◽  
S. Underhill ◽  
Paula Maycock ◽  
Judith A. Fairhurst ◽  
...  

1. Dobutamine in 5% (w/v) d-glucose was infused at sequential doses of 2, 5 and 10 μg min−1 kg−1, 45 min at each dose, into eight healthy male subjects, and the effects were compared with those produced by infusion of the corresponding volumes of 5% (w/v) d-glucose alone. 2. The energy expenditure increased and was 33% higher than control (P<0.001) at 10 μg of dobutamine min−1 kg−1. The respiratory exchange ratio decreased from 0.85 (sem 0.02) before infusion to 0.80 (sem 0.01) at 10 μg of dobutamine min−1 kg−1, but did not alter during the placebo infusion (P> 0.001). 3. Plasma noradrenaline concentrations were lower during the dobutamine infusion compared with during the infusion of d-glucose alone (P < 0.025). Plasma dopamine concentrations remained below 0.1 nmol/l throughout both infusions. 4. Compared with during the placebo infusion, the blood glucose concentration decreased (P < 0.001), the plasma glycerol and free fatty acid concentrations increased by 150 and 225%, respectively (both P < 0.001), and the plasma potassium concentration decreased from 3.8 (sem 0.07) to 3.6 (sem 0.04) mmol/l (P<0.01) during dobutamine infusion. The plasma insulin concentration increased at 2 and 5 μg of dobutamine min−1 kg−1 (P<0.001) with no further rise at 10 μg of dobutamine min−1 kg−1. 5. Compared with during the placebo infusion, the systolic and diastolic blood pressures and the heart rate increased during dobutamine infusion (P<0.01). At 10 μg of dobutamine min−1 kg−1, the systolic blood pressure was around 160 mmHg (P < 0.001) and the heart rate was around 92 (sem 8) beats/min compared with 59 (sem 4) beats/min during the placebo infusion (P < 0.001). 6. Dobutamine has metabolic effects. It is markedly thermogenic and lipolytic. It depresses the respiratory exchange ratio and endogenous noradrenaline secretion, stimulates insulin secretion and depresses the blood glucose concentration.

1990 ◽  
Vol 79 (6) ◽  
pp. 605-611 ◽  
Author(s):  
Cathy J. Regan ◽  
R. Duckworth ◽  
Judith A. Fairhurst ◽  
Paula F. Maycock ◽  
K. N. Frayn ◽  
...  

1. Dopamine in 5% (w/v) d-glucose was infused into five healthy male volunteers at doses of 2, 5 and 10 μg min−1 kg−1 over three sequential periods of 45 min each. 2. Oxygen consumption, respiratory exchange ratio, blood glucose concentration and plasma levels of free fatty acids, glycerol, lactate, dopamine, adrenaline and noradrenaline were measured. The results were compared with values obtained during infusion over the same time period of the corresponding volumes of 5% (w/v) d-glucose alone. 3. Energy expenditure calculated from the oxygen consumption and the respiratory exchange ratio was higher than control values during infusion of dopamine (P < 0.001, analysis of variance) specifically at a rate of 10 μg min−1 kg−1 (P < 0.05) when it was 14% higher, but not at a rate 2 of or 5 μg min−1 kg−1. The plasma noradrenaline concentration was 74 and 230% and the blood glucose concentration was 21 and 36% higher than control values at 5 and 10 μg of dopamine min−1 kg−1, respectively (P < 0.01). At 10 μg of dopamine min−1 kg−1 the plasma free fatty acid concentration was 70% and the plasma glycerol concentration was 80% higher than during the control infusion (P < 0.01). The respiratory exchange ratio and the plasma lactate concentration were the same in the two groups and did not alter during the dopamine infusion. The plasma adrenaline concentration rose significantly (P < 0.01), but only transiently, during dopamine infusion at a rate of 2 μg min−1 kg−1. 4. Dopamine at low doses has metabolic effects. It increases the blood glucose concentration and the circulating noradrenaline level at an infusion rate of 5 μg min−1 kg−1. It increases energy expenditure and circulating free fatty acid and glycerol levels at an infusion rate of 10 μg min−1 kg−1, presumably due to stimulation of lipolysis.


1971 ◽  
Vol 125 (2) ◽  
pp. 541-544 ◽  
Author(s):  
R. A. Hawkins ◽  
K. G. M. M. Alberti ◽  
C. R. S. Houghton ◽  
D. H. Williamson ◽  
H. A. Krebs

1. Sodium acetoacetate was infused into the inferior vena cava of fed rats, 48h-starved rats, and fed streptozotocin-diabetic rats treated with insulin. Arterial blood was obtained from a femoral artery catheter. 2. Acetoacetate infusion caused a fall in blood glucose concentration in fed rats from 6.16 to 5.11mm in 1h, whereas no change occurred in starved or fed–diabetic rats. 3. Plasma free fatty acids decreased within 10min, from 0.82 to 0.64mequiv./l in fed rats, 1.16 to 0.79mequiv./l in starved rats and 0.83 to 0.65mequiv./l in fed–diabetic rats. 4. At 10min the plasma concentration rose from 20 to 49.9μunits/ml in fed unanaesthetized rats and from 6.4 to 18.5μunits/ml in starved rats. There was no change in insulin concentration in the diabetic rats. 5. Nembutal-anaesthetized fed rats had a more marked increase in plasma insulin concentration, from 30 to 101μunits/ml within 10min. 6. A fall in blood glucose concentration in fed rats and a decrease in free fatty acids in both fed and starved rats is to be expected as a consequence of the increase in plasma insulin. 7. The fall in the concentration of free fatty acids in diabetic rats may be due to a direct effect of ketone bodies on adipose tissue. A similar effect on free fatty acids could also be operative in normal fed or starved rats.


1987 ◽  
Vol 72 (6) ◽  
pp. 743-748 ◽  
Author(s):  
I. W. Fellows ◽  
D. F. Evans ◽  
T. Bennett ◽  
I. A. Macdonald ◽  
A. G. Clark ◽  
...  

1. The effect of insulin-induced hypoglycaemia on gastro-jejunal motility was studied in five, healthy, male subjects using tethered, pressure sensitive, radiotelemetry capsules. 2. Thirty minutes after the intravenous injection of soluble insulin (0.15 unit/kg body weight), a significant reduction in blood glucose concentration (control: 5.26 ± 0.19 sem mmol/l; insulin: 1.48 ± 0.44 mmol/l; P < 0.001) was associated with a rise in heart rate (mean peak rise 29 ± 8 beats/min, P < 0.05), systolic arterial blood pressure (mean peak rise 28 ± 4 mmHg, P < 0.01) and plasma pancreatic polypeptide concentration (control: 20 ± 7 pmol/l; insulin: 287 ± 66 pmol/l; P < 0.01). These events coincided with a short period of jejunal motor activity, which was not associated with gastric motor activity nor with raised plasma motilin concentrations. 3. During the control study, there were no changes in blood glucose concentration, heart rate, arterial blood pressure or plasma pancreatic polypeptide concentrations, and there was no jejunal motor activity. 4. The interval between successive gastric migrating motor complexes (MMC) was not significantly different in the insulin and control studies (control: median interval 110 min, range 108–148 min; insulin: median interval 124 min, range 115–125 min), suggesting that the fasting gastro-jejunal MMC and jejunal motor activity arose independently. 5. Insulin-induced hypoglycaemia is accompanied by jejunal motor activity, which may underlie the abdominal symptoms associated with hypoglycaemia.


1991 ◽  
Vol 81 (2) ◽  
pp. 189-194 ◽  
Author(s):  
Stephanie A. Amiel ◽  
Helen R. Archibald ◽  
Gary Chusney ◽  
Alistair J. K. Williams ◽  
Edwin A. M. Gale

1. The effect of hyperketonaemia on counter-regulatory hormone responses to hypoglycaemia has been examined in six healthy subjects. 2. A controlled, step-wise reduction in blood glucose concentration was achieved by adjusting the rate of glucose infusion during a primed-continuous infusion of soluble insulin (1.5 m-units min−1 kg−1 body weight, plasma insulin concentration approximately 90 m-units/l). Simultaneous infusion of either saline or β-hydroxybutyrate (3 mg min−1 kg−1 body weight) was administered in a single-blind fashion, in random order. Despite a need for 40% more glucose during the ketone infusion, an identical fall in blood glucose concentration was achieved in each study. 3. The glycaemic threshold for stimulating an adrenaline response of 0.41 nmol/l was reduced from 3.1 to 2.8 mmol/l (P < 0.05) during ketone infusion, and that for stimulating a response of more than 50% of basal from 3.6 to 3.1 mmol/l (P < 0.001). The peak adrenaline response fell from 7.97 to 2.6 nmol/l (P < 0.04). Peak noradrenaline, cortisol and growth hormone responses were also significantly lower during ketone infusion (P = 0.04, 0.001 and 0.006, respectively). Glucagon responses alone were unaffected by hyperketonaemia. 4. The provision of an alternate metabolic fuel thus produced immediate changes in the neurohumoral responses to hypoglycaemia. This is consistent with the hypothesis that human nervous tissue can metabolize ketones acutely.


1971 ◽  
Vol 50 (2) ◽  
pp. 293-299 ◽  
Author(s):  
M. PEAKER ◽  
STEPHANIE J. PEAKER ◽  
J. G. PHILLIPS ◽  
A. WRIGHT

SUMMARY Ducks given corticotrophin (ACTH) i.m. for 5 days secreted significantly more nasal fluid in response to an i.v. injection of 0·5 m-NaCl. However, blood glucose and plasma potassium concentrations also increased in the birds given ACTH and when these changes in blood composition were produced by injecting glucose or KC1, an effect similar to that of ACTH was obtained, suggesting that glucocorticoids influence the salt gland indirectly rather than, or as well as, directly. The concentrations of Na+ and K+ in the nasal fluid were decreased by ACTH, an effect not mimicked by glucose or KC1, and this might suggest some direct influence on water movements in the salt gland. ACTH increased nasal secretion in response to a minimal stimulatory salt load approximately 15 min after i.v. injection and this increase coincided with a marked rise in blood glucose concentration.


Endocrinology ◽  
2021 ◽  
Vol 162 (4) ◽  
Author(s):  
Jordan B Wean ◽  
Bret N Smith

Abstract Fibroblast growth factor 19 (FGF19) is a protein hormone that produces antidiabetic effects when administered intracerebroventricularly in the forebrain. However, no studies have examined how FGF19 affects hindbrain neurons that participate directly in autonomic control of systemic glucose regulation. Within the dorsal hindbrain, parasympathetic motor neurons of the dorsal motor nucleus of the vagus (DMV) express fibroblast growth factor receptors and their activity regulates visceral homeostatic processes, including energy balance. This study tested the hypothesis that FGF19 acts in the hindbrain to alter DMV neuron excitability and lower blood glucose concentration. Fourth ventricle administration of FGF19 produced no effect on blood glucose concentration in control mice, but induced a significant, peripheral muscarinic receptor-dependent decrease in systemic hyperglycemia for up to 12 h in streptozotocin-treated mice, a model of type 1 diabetes. Patch-clamp recordings from DMV neurons in vitro revealed that FGF19 application altered synaptic and intrinsic membrane properties of DMV neurons, with the balance of FGF19 effects being significantly modified by a recent history of systemic hyperglycemia. These findings identify central parasympathetic circuitry as a novel target for FGF19 and suggest that FGF19 acting in the dorsal hindbrain can alter vagal output to produce its beneficial metabolic effects.


2009 ◽  
Vol 19 (6) ◽  
pp. 645-658 ◽  
Author(s):  
Ian Rollo ◽  
Clyde Williams

The aim of this study was to investigate the influence of ingesting a carbohydrate-electrolyte solution (CHO-E) on performance during a 1-hr treadmill run. Eight male endurance-trained runners (age 31 ± 8 yr, M ± SD) completed three 1-hr performance runs separated by 1 wk. The study used a double-blind placebo (PLA) controlled design. On 2 occasions (P1, P2) runners consumed a placebo solution, 8 ml/kg body mass (BM), 30 min before and 2 ml/kg BM at 15-min intervals throughout the 1-hr run. On a separate occasion they consumed the same quantity of a 6.4% CHO-E solution (C). Total distances covered for P1, P2, and C trials were 13,685 ± 1,116 m, 13,715 ± 1,143 m, and 14,046 ± 1,104 m, respectively. Although there was no difference between the 2 PLA trials (p > .05), the distance covered during the C trial was significantly greater than in either PLA trial (p < .05). CHO ingestion resulted in a higher blood glucose concentration only at the onset of exercise (p < .05) compared with the PLA trials. Blood lactate, respiratory-exchange ratio, and CHO oxidation were similar in all 3 trials. In conclusion, ingestion of a 6.4% CHO-E solution before and during exercise was associated with improved running performance in runners compared with the ingestion of a color- and taste-matched placebo.


2011 ◽  
Vol 17 (3) ◽  
pp. 187-204 ◽  
Author(s):  
J. Parada ◽  
J.M. Aguilera

Starch is the most important source of energy for humans, and it is present in many products derived from cereals, legumes and tubers. Interestingly, some of these food products can have different metabolic effects (e.g. change of postprandial blood glucose concentration) although the total amount of starch is the same. This review focuses on a microstructural perspective of the glycemic response, in search of an alternative and complementary explanation of this phenomenon. Several starch and food microstructures are responsible for the change in starch bioaccessibility. Aspects such as the characterization of the microstructure of starchy products and, its relation to the metabolic problem, the crucial role of the food matrix and other components in the ingested meal, and the gaps in our present knowledge are discussed.


Author(s):  
Tanja Oosthuyse ◽  
Matthew Carstens ◽  
Aletta M.E. Millen

Certain commercial carbohydrate replacement products include slowly absorbed carbohydrates such as isomaltulose. Few studies have investigated the metabolic effects of ingesting isomaltulose during exercise and none have evaluated exercise performance and gastrointestinal comfort. Nine male cyclists participated postprandially during three trials of 2-h steady-state (S-S) exercise (60% Wmax) followed by a 16 km time trial (TT) while ingesting 63 g∙h-1 of either, 0.8:1 fructose: maltodextrin (F:M) or isomaltulose (ISO) or placebo-flavored water (PL). Data were analyzed by magnitude-based inferences. During S-S exercise, ISO and PL similarly increased plasma nonesterified fatty acid (NEFA) concentration (mean change ISO versus F:M: 0.18, 90%CI ± 0.21 mmol∙L-1, 88% likelihood) and fat oxidation (10, 90%CI ± 9 g, 89% likelihood) while decreasing carbohydrate oxidation (-36, 90%CI ± 30.2 g, 91% likelihood) compared with F:M, despite equal elevations in blood glucose concentration with ISO and F:M. Rating of stomach cramps and bloating increased progressively with ISO (rating: 0-90 min S-S, weak; 120 min S-S, moderate; TT, strong) compared with F:M and PL (0-120 min S-S and TT, very weak). TT performance was substantially slower with ISO (mean change: 1.5, 90%CI ± 1.4 min, 94% likely harmful) compared with F:M. The metabolic response of ISO ingestion during moderate exercise to increase NEFA availability and fat oxidation despite elevating blood glucose concentration is anomalous for a carbohydrate supplement. However, ingesting isomaltulose at a continuous high frequency to meet the recommended carbohydrate replacement dose, results in severe gastrointestinal symptoms during prolonged or high intensity exercise and negatively affects exercise performance compared with fructose-maltodextrin supplementation.


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