Lipogenesis from ketone bodies in perfused livers from streptozocin-induced diabetic rats

Diabetes ◽  
1988 ◽  
Vol 37 (1) ◽  
pp. 50-55 ◽  
Author(s):  
L. E. Freed ◽  
G. Endemann ◽  
J. F. Tomera ◽  
V. C. Gavino ◽  
H. Brunengraber
Keyword(s):  
Ketone Bodies ◽  
Diabetic Rats

Uptake of Ketone Bodies in Perfused Hindquarter and Kidney of Starved, Thyrotoxic, and Diabetic Rats

1993 ◽  
Vol 203 (1) ◽  
pp. 55-59 ◽  
Author(s):  
T. Ikeda ◽  
M. Ishimura ◽  
H. Terasawa ◽  
H. Ochi ◽  
I. Ohtani ◽  
...  
Keyword(s):  
Ketone Bodies ◽  
Diabetic Rats

Insulin treatment fails to abolish the teratogenic potential of serum from diabetic rats

1996 ◽  
Vol 134 (4) ◽  
pp. 459-466 ◽  
Author(s):  
Parri Wentzel ◽  
Ulf J Eriksson
Keyword(s):  
Glucose Concentration ◽  
Insulin Treatment ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Normal Serum ◽  
Serum Factors ◽  
Crown Rump Length ◽  
Increased Risk ◽  
Control Serum ◽  
Teratogenic Potential

Wentzel P, Eriksson UJ. Insulin treatment fails to abolish the teratogenic potential of serum from diabetic rats. Eur J Endocrinol 1996;134:459–66. ISSN 0804–4643 Maternal diabetes during pregnancy constitutes an increased risk for congenital malformations in the offspring. Previous studies have identified several serum components with teratogenic activity, e.g. glucose and β-hydroxybutyrate, but have also suggested that the teratogenic influence of the diabetic environment on the developing embryo is multifactorial and may depend upon changed concentrations of several maternal metabolites. In the present investigation we aimed to assess the teratological impact of small, concomitant alterations in a series of metabolites, particularly those not previously identified as teratogens. We thus investigated the influence of a mild diabetic environment by culturing gestational day-9 rat embryos in serum from insulin-treated diabetic rats for 48 h in vitro, and compared the embryonic outcome with that obtained after culture in normal serum and in serum from manifestly diabetic rats without insulin treatment. The glucose concentration was adjusted to 10 or 30 mmol/l in the cultures, and the embryos were evaluated with respect to crown–rump length, protein and DNA content, number of somites and malformation score (comparing major, minor or no malformations). We found that increased glucose levels caused embryonic maldevelopment in both normal and diabetic serum, and that despite normalization of the diabetic state, the serum from the insulin-treated diabetic rats caused more growth retardation than the nondiabetic control serum. The normalized diabetic serum was also more teratogenic than the normal serum at the low glucose concentration, whereas the serum from the manifestly diabetic rats tended to cause more dysmorphogenesis at 30 mmol/l glucose than both the normal and normalized diabetic serum. The results suggest that the teratogenicity of maternal serum in diabetic pregnancy is not mediated exclusively by increased concentrations of glucose and ketone bodies. The efforts to diminish the teratogenic effects of a diabetic environment should therefore include normalization of a multitude of serum factors, including glucose and ketone bodies. Parri Wentzel, Department of Medical Cell Biology, University of Uppsala, Biomedicum, PO Box 571, S-751 23 Uppsala, Sweden

scholarly journals Rates of ketone-body formation in the perfused rat liver

1969 ◽  
Vol 112 (5) ◽  
pp. 595-600 ◽  
Author(s):  
H. A. Krebs ◽  
Patricia G. Wallace ◽  
R. Hems ◽  
R. A. Freedland
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Ketone Bodies ◽  
Short Chain Fatty Acids ◽  
Diabetic Rats ◽  
Isolated Perfused Rat Liver ◽  
Perfused Liver ◽  
Perfused Rat Liver ◽  
Normal Range ◽  
Physiological Value

1. The rates of formation of acetoacetate and β-hydroxybutyrate by the isolated perfused rat liver were measured under various conditions. 2. The rates found after addition of butyrate, octanoate, oleate and linoleate were about 100μmoles/hr./g. wet wt. in the liver of starved rats. These rates are much higher than those found with rat liver slices. 3. The differences between the rates given by slices and by the perfused organ were much higher with the long-chain than with short-chain fatty acids. The increments caused by oleate and linoleate were 12 and 16 times as large in the perfused organ as in the slices, whereas the increments caused by butyrate and octanoate were about four times as large. 4. The rates of ketogenesis in the unsupplemented perfused liver of well-fed rats, and the increments caused by the addition of fatty acids, were about half of those in the liver from starved rats. 5. The value of the [β-hydroxybutyrate]/[acetoacetate] ratio of the medium was raised by octanoate, oleate and linoleate. 6. Carnitine did not significantly accelerate ketogenesis from fatty acids. 7. Oleate formed up to 82% of the expected yield of ketone bodies. 8. In the liver of alloxan-diabetic rats the endogenous rates of ketogenesis were raised, in some cases as high as in the liver from starved rats, after addition of oleate. 9. On addition of either β-hydroxybutyrate or acetoacetate to the perfusion medium the liver gradually adjusted the [β-hydroxybutyrate]/[acetoacetate] ratio towards the normal range. 10. The [β-hydroxybutyrate]/[acetoacetate] ratio of the medium was about 0·4 when slices were incubated, but near the physiological value of 2 when the liver was perfused. 11. The experiments demonstrate that for the study of ketogenesis slices are in many ways grossly inferior to the perfused liver.

scholarly journals Glutamine and ketone-body metabolism in the gut of streptozotocin-diabetic rats

1988 ◽  
Vol 249 (2) ◽  
pp. 565-572 ◽  
Author(s):  
M S M Ardawi
Keyword(s):  
Small Intestine ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Glutamine Metabolism ◽  
Gut Mucosa ◽  
Streptozotocin Induced Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
Short And Long Term

1. In short- and long-term diabetic rats there is a marked increase in size of both the small intestine and colon, which was accompanied by marked decreases (P less than 0.001) and increases (P less than 0.001) in the arterial concentrations of glutamine and ketone bodies respectively. 2. Portal-drained viscera blood flow increased by approx. 14-37% when expressed as ml/100 g body wt., but was approximately unchanged when expressed as ml/g of small intestine of diabetic rats. 3. Arteriovenous-difference measurements for ketone bodies across the gut were markedly increased in diabetic rats, and the gut extracted ketone bodies at approx. 7 and 60 nmol/min per g of small intestine in control and 42-day-diabetic rats respectively. 4. Glutamine was extracted by the gut of control rats at a rate of 49 nmol/min per g of small intestine, which was diminished by 45, 76 and 86% in 7-, 21- and 42-day-diabetic rats respectively. 5. Colonocytes isolated from 7- or 42-day-diabetic rats showed increased and decreased rates of ketone-body and glutamine metabolism respectively, whereas enterocytes of the same animals showed no apparent differences in the rates of acetoacetate utilization as compared with control animals. 6. Prolonged diabetes had no effects on the maximal activities of either glutaminase or ketone-body-utilizing enzymes of colonic tissue preparations. 7. It is concluded that, although the epithelial cells of the small intestine and the colon during streptozotocin-induced diabetes exhibit decreased rates of metabolism of glutamine, such decreases were partially compensated for by enhanced ketone-body utilization by the gut mucosa of diabetic rats.

scholarly journals Relationship between plasma and muscle concentrations of ketone bodies and free fatty acids in fed, starved and alloxan-diabetic states

1973 ◽  
Vol 134 (2) ◽  
pp. 499-506 ◽  
Author(s):  
Oliver E. Owen ◽  
Helene Markus ◽  
Stuart Sarshik ◽  
Maria Mozzoli
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Plasma Glucose ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Water Concentration ◽  
Diabetic Rats ◽  
Muscle Membrane

1. Concentrations of ketone bodies, free fatty acids and chloride in fed, 24–120h-starved and alloxan-diabetic rats were determined in plasma and striated muscle. Plasma glucose concentrations were also measured in these groups of animals. 2. Intracellular metabolite concentrations were calculated by using chloride as an endogenous marker of extracellular space. 3. The mean intracellular ketone-body concentrations (±s.e.m.) were 0.17±0.02, 0.76±0.11 and 2.82±0.50μmol/ml of water in fed, 48h-starved and alloxan-diabetic rats, respectively. Mean (intracellular water concentration)/(plasma water concentration) ratios were 0.47, 0.30 and 0.32 in fed, 48h-starved and alloxan-diabetic rats respectively. The relationship between ketone-body concentrations in the plasma and intracellular compartments appeared to follow an asymptotic pattern. 4. Only intracellular 3-hydroxybutyrate concentrations rose during starvation whereas concentrations of both 3-hydroxybutyrate and acetoacetate were elevated in the alloxan-diabetic state. 5. During starvation plasma glucose concentrations were lowest at 48h, and increased with further starvation. 6. There was no significant difference in the muscle intracellular free fatty acid concentrations of fed, starved and alloxan-diabetic rats. Mean free fatty acid intramuscular concentrations (±s.e.m.) were 0.81±0.08, 0.98±0.21 and 0.91±0.10μmol/ml in fed, 48h-starved and alloxan-diabetic states. 7. The intracellular ketosis of starvation and the stability of free fatty acid intracellular concentrations suggests that neither muscle membrane permeability nor concentrations of free fatty acids per se are major factors in limiting ketone-body oxidation in these states.

Food intake in diabetic rats: isolation of primary metabolic effects of fat feeding

1985 ◽  
Vol 249 (1) ◽  
pp. R44-R51 ◽  
Author(s):  
M. I. Friedman ◽  
I. Ramirez ◽  
N. K. Edens ◽  
J. Granneman
Keyword(s):  
Food Intake ◽  
Food Consumption ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Metabolic Effects ◽  
Carbohydrate Consumption ◽  
Plasma Triglycerides ◽  
Urinary Glucose ◽  
Ad Libitum ◽  
Fat Feeding

The effects of varying dietary fat content on food intake and metabolism in streptozotocin-diabetic rats were examined. The metabolic consequences of fat feeding were separated from the marked adjustments in voluntary food consumption that occur when diabetic rats are fed diets containing different amounts of fat by feeding rats a fixed ration of food in which either fats or carbohydrates were reduced by equicaloric amounts, or in which only the concentration of fat, but not other dietary nutrients, was varied systematically. Resulting changes in metabolism and subsequent ad libitum food intake on refeeding were then measured. Rats did not increase their food intake after a prior reduction in carbohydrate consumption but did so after an equicaloric reduction in fat consumption. Urinary glucose excretion during rationing was a function of carbohydrate consumption and was not predictive of changes in food intake during refeeding. The more fat that rats consumed during rationing, the higher their levels of plasma triglycerides and ketone bodies were at the time of refeeding and the less they ate when allowed to eat ad libitum. The orderly changes in food consumption and in plasma triglycerides and ketones observed with variations in fat intake suggest that the effects of fat feeding on food intake in diabetic rats are mediated through the oxidation of ingested fat.

2,5-anhydro-D-mannitol: a fructose analogue that increases food intake in rats

1988 ◽  
Vol 254 (1) ◽  
pp. R150-R153 ◽  
Author(s):  
M. G. Tordoff ◽  
R. Rafka ◽  
M. J. DiNovi ◽  
M. I. Friedman
Keyword(s):  
Fatty Acids ◽  
Food Intake ◽  
Free Fatty Acids ◽  
Plasma Glucose ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Substrate Analogues ◽  
Increase Food Intake ◽  
Related Increase

We examined the effects on food intake and plasma fuels of 2,5-anhydro-D-mannitol (2,5-AM; 2-deoxy-D-fructose), a fructose analogue that inhibits hepatocyte gluconeogenesis and glycogenolysis in vitro. 2,5-AM (50-800 mg/kg po) given to rats during the diurnal fast produced a dose-related increase in food intake during the 2 h after administration. A 200-mg/kg dose of 2,5-AM decreased plasma glucose, increased plasma ketone bodies, free fatty acids, and glycerol, and had no effect on triglycerides. Normal and diabetic rats given 2,5-AM (200 mg/kg ip) increased food intake to the same extent. These results suggest that, unlike other substrate analogues that increase food intake, 2,5-AM increases feeding by creating a metabolic state that resembles fasting.

scholarly journals A possible mechanism for the anti-ketogenic action of alanine in the rat

1980 ◽  
Vol 190 (2) ◽  
pp. 323-332 ◽  
Author(s):  
Romano Nosadini ◽  
Harish Datta ◽  
Alan Hodson ◽  
K. George M. M. Alberti
Keyword(s):  
Ketone Body ◽  
Ketone Bodies ◽  
Regulatory System ◽  
Glucagon Secretion ◽  
Diabetic Rats ◽  
Metabolic Clearance ◽  
Endogenous Insulin ◽  
Feedback Cycle ◽  
Insulin And Glucagon Secretion ◽  
Acetoacetate Infusion

1. The anti-ketogenic effect of alanine has been studied in normal starved and diabetic rats by infusing l-alanine for 90min in the presence of somatostatin (10μg/kg body wt. per h) to suppress endogenous insulin and glucagon secretion. 2. Infusion of alanine at 3mmol/kg body wt. per h caused a 70±11% decrease in [3-hydroxybutyrate] and a 58±9% decrease in [acetoacetate] in 48h-starved rats. [Glucose] and [lactate] increased, but [non-esterified fatty acid], [glycerol] and [3-hydroxybutyrate]/[acetoacetate] were unchanged. 3. Infusion of alanine at 1mmol/kg body wt. per h caused similar decreases in [ketone body] (3-hydroxybutyrate plus acetoacetate) in 24h-starved normal and diabetic rats, but no change in other blood metabolites. 4. Alanine [3mmol/kg body wt. per h] caused a 72±9% decrease in the rate of production of ketone bodies and a 57±8% decrease in disappearance rate as assessed by [3-14C]acetoacetate infusion. Metabolic clearance was unchanged, indicating that the primary effect of alanine was inhibition of hepatic ketogenesis. 5. Aspartate infusion at 6mmol/kg body wt. per h had similar effects on blood ketone-body concentrations in 48h-starved rats. 6. Alanine (3mmol/kg body wt. per h) caused marked increases in hepatic glutamate, aspartate, malate, lactate and citrate, phosphoenolpyruvate, 2-phosphoglycerate and glucose concentrations and highly significant decreases in [3-hydroxybutyrate] and [acetoacetate]. Calculated [oxaloacetate] was increased 75%. 7. Similar changes in hepatic [malate], [aspartate] and [ketone bodies] were found after infusion of 6mmol of aspartate/kg body wt. per h. 8. It is suggested that the anti-ketogenic effect of alanine is secondary to an increase in hepatic oxaloacetate and hence citrate formation with decreased availability of acetyl-CoA for ketogenesis. The reciprocal negative-feedback cycle of alanine and ketone bodies forms an important non-hormonal regulatory system.

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