Ketone infusion lowers hormonal responses to hypoglycaemia: Evidence for acute cerebral utilization of a non-glucose fuel

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 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.


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.


2010 ◽  
Vol 80 (2) ◽  
pp. 87-96 ◽  
Author(s):  
Jung Yun Kim ◽  
Sang Sun Lee

The purpose of this study was to investigate whether the genetic polymorphisms of the uncoupling protein 1 (UCP1) and beta 3 adrenergic receptor (β3-AR) were associated with differences in weight loss and lipid profiles in obese premenopausal women exposed to low-calorie meal replacements over a period of six weeks. Forty women between the ages of 20 and 35 were randomly divided into two groups, each of which consumed one of two low-calorie meal replacements containing either white rice or mixed rice. Although body weight, body mass index (BMI), blood glucose concentration, triglycerides, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were not significantly different by the UCP1 genotype in the white rice group, there were significant differences in body weight (p = 0.041), BMI (p = 0.027), and blood glucose concentration (p = 0.047) between carriers and non-carriers of the G allele in the mixed rice group after the six-week meal replacement intervention. The β3-AR polymorphism showed no apparent affect on these parameters. Dietary fiber affects weight gain since it is closely related with absorption of nutrients. As a result, the AA type UCP1 genotype produced significant weight loss in the mixed rice group, but not in the white rice group.


1999 ◽  
Vol 276 (3) ◽  
pp. G761-G766 ◽  
Author(s):  
M. A. M. T. Verhagen ◽  
C. K. Rayner ◽  
J. M. Andrews ◽  
G. S. Hebbard ◽  
S. M. Doran ◽  
...  

Marked hyperglycemia (blood glucose ∼14 mmol/l) slows gastric emptying and affects the perception of sensations arising from the gut. Elevation of blood glucose within the physiological range also slows gastric emptying. This study aimed to determine whether physiological changes in blood glucose affect proximal gastric compliance and/or the perception of gastric distension in the fasting state. Paired studies were conducted in 10 fasting healthy volunteers. On a single day, isovolumetric and isobaric distensions of the proximal stomach were performed using an electronic barostat while the blood glucose concentration was maintained at 4 and 9 mmol/l in random order. Sensations were quantified using visual analog scales. The blood glucose concentration had no effect on the pressure-volume relationship during either isovolumetric or isobaric distensions or the perception of gastric distension. At both blood glucose concentrations, the perceptions of fullness, nausea, bloating, and abdominal discomfort, but not hunger or desire to eat, were related to intrabag volume ( P ≤ 0.002) and pressure ( P ≤ 0.01). We conclude that, in the fasted state, elevations of blood glucose within the physiological range do not affect proximal gastric compliance or the perception of gastric distension.


1993 ◽  
Vol 85 (5) ◽  
pp. 537-542 ◽  
Author(s):  
K. T. Moriarty ◽  
E. J. Simpson ◽  
N. S. Brown ◽  
I. A. MaCdonald ◽  
R. B. Tattersall

1. This study was designed to determine whether a 1 h period of mild hypoglycaemia (33 or 3.7 mmol/l) affected the response to an episode of moderate hypoglycaemia (2.5 mmol/l) immediately afterwards. 2. Eleven non-obese healthy men (age 26 + 1 years, mean + SEM) underwent three separate 3 h hyperinsulinaemic glucose clamps in single-blind, random order. On all three occasions, blood glucose was 4.5 mmol/l for the first hour, and on a control visit was maintained at this level for the second hour. In the other two visits, blood glucose was lowered to 3.7 or 33 mmol/l during the second hour. In the third hour, blood glucose was lowered to 2.5 mmol/l on all three visits. 3. In the second hour, adrenaline rose significantly (P <0.05, analysis of variance) with a blood glucose of 33 and 3.7 mmol/l, as did cortisol and heart rate at 33 mmol/l, but glucagon, prolactin, sweating rate, symptom score and blood pressure were the same during the second hour on all three visits. 4. In the final hour at 2.5 mmol/l, there were no differences in adrenaline, noradrenaline, glucagon, prolactin, cortisol, symptom score, heart rate, blood pressure or sweating rate. 5. Thus, the overall magnitude of hormonal responses to moderate hypoglycaemia (2.5 mmol/l) are not modified by exposure to mild hypoglycaemia (33 or 3.7 mmol/l) for 1 h immediately beforehand.


Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1078
Author(s):  
Rabie Kamal ◽  
Mourad Kharbach ◽  
Yvan Vander Heyden ◽  
Huiwen Yu ◽  
Abdelaziz Bouklouze ◽  
...  

The Argan tree (Argania spinosa. L) is an evergreen tree endemic of southwestern Morocco. For centuries, various formulations have been used to treat several illnesses including diabetes. However, scientific results supporting these actions are needed. Hence, Argan fruit products (i.e., cake byproducts (saponins extract) and hand pressed Argan oil) were tested for their in-vitro anti-hyperglycemic activity, using α-glucosidase and α-amylase assays. The in-vivo anti-hyperglycemic activity was evaluated in a model of alloxan-induced diabetic mice. The diabetic animals were orally administered 100 mg/kg body weight of aqueous saponins cake extract and 3 mL/kg of Argan oil, respectively, to evaluate the anti-hyperglycemic effect. The blood glucose concentration and body weight of the experimental animals were monitored for 30 days. The chemical properties and composition of the Argan oil were assessed including acidity, peroxides, K232, K270, fatty acids, sterols, tocopherols, total polyphenols, and phenolic compounds. The saponins cake extract produced a significant reduction in blood glucose concentration in diabetic mice, which was better than the Argan oil. This decrease was equivalent to that detected in mice treated with metformin after 2–4 weeks. Moreover, the saponins cake extract showed a strong inhibitory action on α-amylase and α-glucosidase, which is also higher than that of Argan oil.


2021 ◽  
pp. 193229682110538
Author(s):  
Jiali Xu ◽  
James W. McKeage ◽  
Bryan P. Ruddy ◽  
Poul M. F. Nielsen ◽  
Andrew J. Taberner

Background: Lancet pricks are often poorly received by individuals with diabetes; jet injection may allow lancet-free blood sampling. We examine whether the technique of jet injection can release sufficient blood from the fingertip to enable measurement of blood glucose concentration. In addition, we assess the effect of jet shape and cross-sectional area on fluid release, blood dilution, and perceived pain. Methods: A randomized, single-blind, crossover study was conducted on 20 healthy volunteers who received interventions on four fingertips: a lancet prick, and jet injection of a small quantity of saline solution through three differently shaped and sized nozzles. Released fluid volume, blood concentration, and glucose concentration were assessed immediately after the intervention. Pain perception and duration, and any skin reactions, were evaluated both immediately and 24 hours after the intervention. Results: Jet injection released sufficient blood from the fingertip to conduct a glucose measurement. A slot-shaped nozzle released the most blood, although less than a lancet, with slightly higher pain. The blood glucose levels estimated from the extracted fluid showed a mean absolute percentage error of 25%. There was no consistent evidence that a jet injection leads to different skin reactions at the intervention site relative to a lancet prick. Conclusions: Fingertip penetration by jet injection can release a volume of fluid sufficient for blood glucose measurement. Jet injection with a slot-shaped nozzle and/or a nozzle with larger outlet area helps to release more fluid. This technique may enable blood sampling, glucose concentration measurement, and insulin delivery to be performed in a single device.


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