scholarly journals The effect of acetoacetate on plasma insulin concentration

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.

1988 ◽  
Vol 59 (2) ◽  
pp. 315-322 ◽  
Author(s):  
Susan Southon ◽  
Susan J. Fairweather-Tait ◽  
Christine M. Williams

1. Wistar rats were fed on a control semi-synthetic diet throughout pregnancy, or a control diet in the first 2 weeks and a marginal-zinc diet in the 3rd week of pregnancy. On day 20, after an overnight fast, half the animals in each group were given glucose by gavage and the 0–30 min rise in blood glucose measured in tail blood. After 60 min blood was taken by cardiac puncture for glucose and insulin assay. Maternal pancreases were removed and the Zn contents measured. Fetuses from each litter were combined for wet/dry weights, protein and DNA determinations.2. Plasma insulin concentration was higher, and glucose concentration and pancreatic Zn content lower, in pregnantv. non-pregnant animals of similar age, fed on the same diet. Pancreatic Zn content was lowest in the marginal-Zn group of pregnant rats. Fetuses from mothers fed on the marginal-Zn diet during the last week of pregnancy were slightly heavier than controls and had a significantly higher protein: DNA ratio. The 0–30 min rise in blood glucose was significantly greater in the marginal-Zn animals.3. In a second experiment, pregnant rats were given similar diets to those used in the first study, but the marginal-Zn diet was given for a shorter period (days 15–19 of pregnancy). On day 19 the rats were meal-fed and on day 20, after an overnight fast, an oral glucose dose was administered. Tail-blood was taken at timed intervals up to 60 min post-dosing for glucose assay. Both maternal and fetal blood glucose and insulin concentration was measured 70 min post-dosing.4. Values for maternal and fetal blood glucose and plasma insulin, measured 70 min after the administration of a glucose dose, were similar in the two groups, but the initial rise in blood glucose concentration was again significantly higher in pregnant rats given the marginal-Zn diet towards term.5. It is suggested that the change in growth and composition, observed in fetuses from rats given a marginal-Zn diet in later pregnancy, is associated with altered maternal carbohydrate metabolism.


2002 ◽  
Vol 282 (2) ◽  
pp. E402-E411 ◽  
Author(s):  
Chang An Chu ◽  
Stephanie M. Sherck ◽  
Kayano Igawa ◽  
Dana K. Sindelar ◽  
Doss W. Neal ◽  
...  

The aim of this study was to determine the effect of high levels of free fatty acids (FFA) and/or hyperglycemia on hepatic glycogenolysis and gluconeogenesis. Intralipid was infused peripherally in 18-h-fasted conscious dogs maintained on a pancreatic clamp in the presence (FFA + HG) or absence (FFA + EuG) of hyperglycemia. In the control studies, Intralipid was not infused, and euglycemia (EuG) or hyperglycemia (HG) was maintained. Insulin and glucagon were clamped at basal levels in all four groups. The arterial blood glucose level increased by 50% in the HG and FFA + HG groups. It did not change in the EuG and FFA + EuG groups. Arterial plasma FFA increased by ∼140% in the FFA + EuG and FFA + HG groups but did not change significantly either in the EuG or HG groups. Arterial glycerol levels increased by ∼150% in both groups. Overall (3-h) net hepatic glycogenolysis was 196 ± 26 mg/kg in the EuG group. It decreased by 96 ± 20, 82 ± 16, and 177 ± 22 mg/kg in the HG, FFA + EuG, and FFA + HG groups, respectively. Overall (3-h) hepatic gluconeogenic flux was 128 ± 22 mg/kg in the EuG group, but it was suppressed by 30 ± 9 mg/kg in response to hyperglycemia. It was increased by 59 ± 12 and 56 ± 10 mg/kg in the FFA + EuG and FFA + HG groups, respectively. In conclusion, an increase in plasma FFA and glycerol significantly inhibited hepatic glycogenolysis and markedly stimulated hepatic gluconeogenesis.


2008 ◽  
Vol 86 (9) ◽  
pp. 643-649 ◽  
Author(s):  
Thomas P. Johnston ◽  
David J. Waxman

Poloxamer 407 (P-407) is a copolymer surfactant that induces a dose-controlled dyslipidemia in both mice and rats. Human macrophages cultured with P-407 exhibit a concentration-dependent reduction in cholesterol efflux to apolipoprotein A1 (apoA1) linked to downregulation of the ATP-binding cassette transporter A1 (ABCA1). Activators of peroxisome proliferator-activated receptor gamma (PPARγ), as well as PPARα, increase expression of liver X receptor alpha (LXRα) in macrophages and promote the expression of ABCA1, which, in turn, mediates cholesterol efflux to apoA1. The present study investigated whether P-407 interferes with this signaling pathway. A transactivation assay was used to evaluate whether P-407 can either activate or inhibit the transcriptional activity of PPARγ. Because thiazolidinedione drugs (PPARγ agonists) improve glycemic control in type 2 diabetes by reducing blood glucose concentrations, P-407 was also evaluated for its potential to alter plasma insulin and blood glucose concentrations in wild-type (C57BL/6) and PPARγ-deficient mice. Additionally, because thiazolidinediones attenuate release of free fatty acids (FFAs) from adipocytes and, consequently, decrease circulating plasma levels of FFAs, plasma concentrations of circulating FFAs were also determined in P-407-treated mice. P-407 was unable to modulate PPARγ activity in cell-based transactivation assays. Furthermore, P-407 did not perturb plasma insulin and blood glucose concentrations after administration to mice. However, by an as yet unidentified mechanism, P-407 caused a significant increase in the serum concentration of FFAs in mice beginning 3 h after administration and lasting more than 24 h postdosing. It is concluded that P-407 does not interfere with the functional activity of PPARγ after administration to mice.


Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 754
Author(s):  
Karah J. Dring ◽  
Simon B. Cooper ◽  
Ryan A. Williams ◽  
John G. Morris ◽  
Caroline Sunderland ◽  
...  

High-intensity intermittent exercise (HIIE) is a potential intervention to manage hyperglycaemia and insulin resistance in adolescents. The aim of this study was to determine the optimum duration of HIIE to reduce postprandial glycaemic and insulinaemic responses in adolescents and the longevity of the response. Thirty-nine participants (12.4 ± 0.4 year) completed a 30- and 60-min exercise trial (Loughborough Intermittent Shuttle Test) and a rested control trial in a randomised crossover design. Capillary blood samples were taken at baseline, immediately and 1-h post-exercise; and 30, 60 and 120 min following a standardised lunch (day one) and a standardised breakfast 24-h post-exercise. Plasma insulin total area under the curve (tAUC) following lunch was lower following 60-min HIIE (21,754 ± 16,861 pmol·L−1 × 120 min, p = 0.032) and tended to be lower following 30-min HIIE (24,273 ± 16,131 pmol·L−1 × 120 min, p = 0.080), when compared with the resting condition (26,931 ± 21,634 pmol·L−1 × 120 min). Blood glucose concentration was lower 1-h post-exercise following 30-min HIIE (3.6 ± 0.6 mmol·L−1) when compared to resting (4.1 ± 0.9 mmol·L−1, p = 0.001). Blood glucose and plasma insulin concentration did not differ across trials on day two. Shorter bouts of HIIE (30-min), as well as a 60-min bout, reduced the postprandial insulinaemic response to lunch, an ecologically valid marker of insulin sensitivity. As the beneficial effects of HIIE were limited to 3 h post-exercise, adolescents are recommended to engage daily HIIE to enhance metabolic health.


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.


Author(s):  
ANDREANYTA MELIALA ◽  
YUSTINA ANDWI ARI SUMIWI ◽  
PARAMITA NARWIDINA ◽  
SRI LESTARI SULISTYO RINI ◽  
WIDIASTUTI SETYANINGSIH

Objective: This study aimed to evaluate the antidiabetic and antidepressant effects of banana peel flakes in streptozotocin-induced diabetic rats. Methods: Twenty-five male Wistar rats were classified into five groups with different treatments. Groups I to IV were diabetic rats model groups that consumed only standard diet, standard diet containing 5%, 10%, and 20% of banana peel flakes, respectively. While group V was a healthy control group fed a standard diet. Immunohistochemistry staining was measured to examine serotonin expression in the colon and pancreas. Results: The diabetic rats treated with 20% banana peel flakes had a lower blood glucose concentration (p<0.05) compared with diabetic control and showed a shorter duration of immobility time (p<0.05) than the healthy control. Additionally, compared with diabetic control, the diabetic rats treated with 5% banana peel flakes showed higher serotonin expression (p<0.05) in the colon. In contrast, serotonin expression in the pancreas did not show any significant difference (p>0.05). Conclusion: The present study disclosed that the banana peel flakes provided an antidepressant effect in the diabetic rats model, which might occur through the mechanism of controlling blood glucose concentration.


1976 ◽  
Vol 50 (3) ◽  
pp. 153-163 ◽  
Author(s):  
C. Weinkove ◽  
E. A. Weinkove ◽  
B. L. Pimstone

1. Young Wistar rats were used as an experimental model to determine the effects of protein-energy malnutrition on glucose tolerance and insulin release. 2. Malnourished rats presented some of the features commonly found in human protein-energy malnutrition, such as failure to gain weight, hypoalbuminaemia, fatty infiltration of the liver and intolerance of oral and intravenous glucose loads. 3. The rate of disappearance of glucose from the gut lumen was greater in the malnourished rats but there was no significant difference in portal blood glucose concentration between normal and malnourished rats 5 and 10 min after an oral glucose load. 4. Insulin resistance was not thought to be the cause of the glucose intolerance in the malnourished animals since these rats had a low fasting plasma insulin concentration with a normal fasting blood glucose concentration and no impairment in their hypoglycaemic response to exogenous insulin administration. Furthermore, fasting malnourished rats were unable to correct the insulin-induced hypoglycaemia despite high concentrations of hepatic glycogen. 5. Malnourished rats had lower peak plasma insulin concentrations than normal control animals after provocation with oral and intravenous glucose, intravenous tolbutamide and intravenous glucose plus aminophyllin. This was not due to a reduction in the insulin content of the pancreas or potassium deficiency. Healthy weanling rats, like the older malnourished rats, had a diminished insulin response to intravenous glucose and intravenous tolbutamide. However, their insulin response to stimulation with intravenous glucose plus aminophyllin far exceeded that of the malnourished rats. Thus the impairment of insulin release demonstrated in the malnourished rats cannot be ascribed to a ‘functional immaturity’ of the pancreas.


1973 ◽  
Vol 58 (3) ◽  
pp. 613-625 ◽  
Author(s):  
D. M. ANDERSON

SUMMARY Pigs were fasted for 18, 39, or 72 h; they were then given two glucose infusions, the second infusion 40 min after the first. Either 0·15, 0·30 or 0·75 g glucose/kg were given at each infusion. Plasma glucose, free fatty acids, insulin and 3-hydroxybutyrate concentrations were measured. The rate of glucose removal Kt was calculated after the first infusions, (Kt1), and after the second infusion (Kt2). When food was withheld the peak insulin concentration decreased in response to glucose but lack of food only affected the mean increase in insulin concentration when 0·75 g glucose/kg was given. The value of Kt1 decreased as the period without food increased and additions of insulin did not affect the difference in Kt1 between animals fasted for 18 h and those fasted for 72 h. Plasma insulin concentration was closely related to the rate of glucose removal; the correlation coefficient (r) for maximum rate of glucose removal versus maximum insulin concentration was 0·9; and that for mean rate of glucose removal versus mean increment in insulin concentration was 0·84. It is suggested that insulin does not itself determine the rate of glucose removal but is secreted in response to the amount of glucose removed. In the pig, the Staub—Traugott phenomenon was found to occur only under special circumstances. The relationship between Kt1 and Kt2 depended on the amount of glucose infused and the time during which food was withheld. Kt2 ranged from smaller than—through the same as—to greater than Kt1. The concentrations of free fatty acids, ketones or insulin did not explain the differences.


1990 ◽  
Vol 258 (1) ◽  
pp. E32-E39 ◽  
Author(s):  
S. Klein ◽  
O. B. Holland ◽  
R. R. Wolfe

The importance of the decline in blood glucose concentration on lipolysis and the lipolytic effect of epinephrine was evaluated during short-term fasting. Lipolytic rates were determined by infusing [2H5]glycerol and [1-13C]palmitic acid. Five volunteers were studied after 12 h of fasting before and during epinephrine infusion and after 84 h of fasting, before and during glucose infusion when plasma glucose was restored to postabsorptive values, and during glucose plus epinephrine infusion. In another protocol, five volunteers were given glucose intravenously throughout fasting to maintain plasma glucose at postabsorptive levels and isotopic studies were performed after 12 and 84 h of fasting before and during epinephrine infusion. Glucose infusion after 84 h of fasting restored glucose and insulin concentrations and lipolytic rates toward 12-h fasting values. When euglycemia was maintained throughout fasting, plasma insulin still declined (P less than 0.05) and lipolytic rates still increased (P less than 0.05). Despite similar glucose concentrations, the lipolytic response to epinephrine infusion was greater after 84 h than after 12 h of fasting in both protocols (P less than 0.05). These studies demonstrate that the decline in plasma glucose contributes to, but is not required for, the increase in lipolysis during fasting. The increase in epinephrine-stimulated lipolysis that occurs during fasting is not dependent on a decrease in plasma glucose concentration.


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