Antiketogenic effect of glucose per se in vivo in man and in vitro in isolated rat liver cells

Riou, Jean‐Paul; Beylot, M.; Laville, Martine; Parscau, L. De; Delinger, J.; Sautot, G; Mornex, R

doi:10.1016/0026-0495(86)90165-4

Cited by 14 publications

(6 citation statements)

References 27 publications

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“…We have not found it necessary to eliminate carbohydrates completely from the ketogenic diet. Whereas glucose decreases ketogenesis (21), it has been shown that carbohydrates can stimulate ketone metabolism, at least in brain slices (22). Although such stimulation would be expected to reduce ketone levels and, from our own data, seizure threshold, it may be that ketone metabolism is important to seizure protection (23).…”

Section: Dietmentioning

confidence: 73%

A Ketogenic Diet Increases the Resistance to Pentylenetetrazole‐Induced Seizures in the Rat

Bough¹,

Eagles²

1999

Epilepsia

136

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Summary:Purpose: The purpose of this study was to test the hypothesis that a ketogenic diet would increase the resistance of rats to pentylenetetrazole (PTZ)-induced seizures and to understand the relation of ketonemia to seizure resistance.Methods: A freely consumed, high-fat (ketogenic) diet was administered to male Sprague-Dawley rats for 5-10 weeks, while control animals were fed either rodent chow or a highcarbohydrate diet. Ketonemia was measured as plasma levels of P-hydroxybutyric acid (P-OHB). Seizures were induced by tail-vein infusion of pentylenetetrazole.Results: The ketogenic diet produced a highly significant (p < 0.01) increase in P-OHB levels within 5 days. Induction ofseizures by PTZ 35 days after animals were placed on their respective diets showed that ketogenic animals had a significantly (p < 0.01) increased threshold for seizure induction compared with those fed an isocaloric diet of either highcarbohydrate or normal rodent chow. Ketogenic animals did not exhibit increased seizure severity relative to controls, despite receiving consistently higher doses of PTZ. Conclusions:The ketogenic diet resulted in an increased seizure threshold, confirming the hypothesis, and seizure threshold was found to be a direct function of the level of ketonemia. Key Words: Rat-Seizure-Threshold-Ketogenic diet-Pentylenetetrazole.Historical accounts have described improved seizure control with abstinence from food and drink (1,2). In an attempt to mimic the physiology of fasting, Wilder (3) formulated a high-fat, low-carbohydrate, low-protein diet (a ketogenic diet) to determine whether seizure control could be attained. Wilder and others subsequently showed that the ketogenic diet was an effective means for treating epilepsy in children (3-7). Despite the reported clinical success of the diet in the early years, the development of efficacious antiepileptic drugs (AEDs) led to its near-abandonment, clinically, resulting in few studies into the mechanism of action of the ketogenic diet.The purpose of this study was to determine whether a ketogenic diet would protect rats from a chemically induced seizure and to define the relation between ketonemia and seizure protection. In both clinical (8,9) and animal (10,ll) studies, ketonemia has been shown to result from consumption of high-fat diets. Huttenlocher (12) suggested that it was the basis of the seizure pro-

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Section: Dietmentioning

confidence: 73%

A Ketogenic Diet Increases the Resistance to Pentylenetetrazole‐Induced Seizures in the Rat

Bough¹,

Eagles²

1999

Epilepsia

136

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“…By contrast, in the absence ofglucose, ketogenesis was at least 3 times as high as with 20 mM-glucose, and the strongest inhibition ofketogenesis was then obtained with alanine and asparagine, followed by proline and glutamine ( Table 1). The anti-ketogenic effect of glucose [22] and alanine [23,24] has previously been described. However, the biochemical reason for the difference in anti-ketogenic capacity of amino acids reported here is not clear.…”

Section: Resultsmentioning

confidence: 95%

Comparison of the effects of various amino acids on glycogen synthesis, lipogenesis and ketogenesis in isolated rat hepatocytes

Baquet¹,

Lavoinne²,

Hue³

1991

Biochemical Journal

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Several amino acids were found to stimulate glycogen synthesis and lipogenesis, and to inhibit ketogenesis in isolated rat hepatocytes. When hepatocytes were incubated in the presence of 20 mM-glucose, the amino acids could be classified in decreasing order of efficiency as follows: glutamine and proline, alanine, aminoisobutyric acid, asparagine and histidine for stimulation of glycogen synthesis; glutamine, proline and alanine for stimulation of lipogenesis; proline and glutamine for inhibition of ketogenesis. The study of the time course revealed that the rates were not linear and were preceded by a lag period. In all conditions studied, glutamine and proline were found to have similar quantitative effects on glycogen synthesis and lipid metabolism. However, their effects differ qualitatively. Indeed, the effects of proline on glycogen synthesis, lipogenesis and glutamate and aspartate content were faster. Moreover, proline increased the hydroxybutyrate/acetoacetate ratio, whereas glutamine did not change it. Incubation of hepatocytes with aminoisobutyric acid or under hypo-osmotic conditions, which increased cell volume and mimicked the amino acid-induced stimulation of glycogen synthesis, had little effect on lipogenesis. In hepatocytes incubated without glucose, ketogenesis was inhibited, in decreasing order of efficiency, by alanine, asparagine, glutamine and proline. Under these conditions, glutamine increased, alanine decreased and asparagine did not affect the concentration of malonyl-CoA. This indicates that the latter cannot be responsible for the inhibition of ketogenesis by alanine and asparagine.

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“…Taken together with our present findings, these data suggest that impaired hepatic mitochondrial fluxes may occur with severe insulin resistance/diabetes but not in the milder setting of diet-induced insulin resistance studied here. It is possible that the induction of frank hyperglycemia itself could impair hepatic ketogenesis during severe insulin resistance (45).…”

Section: Discussionmentioning

confidence: 99%

Progressive adaptation of hepatic ketogenesis in mice fed a high-fat diet

Sunny

Satapati

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Hepatic ketogenesis provides a vital systemic fuel during fasting because ketone bodies are oxidized by most peripheral tissues and, unlike glucose, can be synthesized from fatty acids via mitochondrial beta-oxidation. Since dysfunctional mitochondrial fat oxidation may be a cofactor in insulin-resistant tissue, the objective of this study was to determine whether diet-induced insulin resistance in mice results in impaired in vivo hepatic fat oxidation secondary to defects in ketogenesis. Ketone turnover (micromol/min) in the conscious and unrestrained mouse was responsive to induction and diminution of hepatic fat oxidation, as indicated by an eightfold rise during the fed (0.50+/-0.1)-to-fasted (3.8+/-0.2) transition and a dramatic blunting of fasting ketone turnover in PPARalpha(-/-) mice (1.0+/-0.1). C57BL/6 mice made obese and insulin resistant by high-fat feeding for 8 wk had normal expression of genes that regulate hepatic fat oxidation, whereas 16 wk on the diet induced expression of these genes and stimulated the function of hepatic mitochondrial fat oxidation, as indicated by a 40% induction of fasting ketogenesis and a twofold rise in short-chain acylcarnitines. Together, these findings indicate a progressive adaptation of hepatic ketogenesis during high-fat feeding, resulting in increased hepatic fat oxidation after 16 wk of a high-fat diet. We conclude that mitochondrial fat oxidation is stimulated rather than impaired during the initiation of hepatic insulin resistance in mice.

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Antiketogenic effect of glucose per se in vivo in man and in vitro in isolated rat liver cells

Cited by 14 publications

References 27 publications

A Ketogenic Diet Increases the Resistance to Pentylenetetrazole‐Induced Seizures in the Rat

A Ketogenic Diet Increases the Resistance to Pentylenetetrazole‐Induced Seizures in the Rat

Comparison of the effects of various amino acids on glycogen synthesis, lipogenesis and ketogenesis in isolated rat hepatocytes

Progressive adaptation of hepatic ketogenesis in mice fed a high-fat diet

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