Extraction of D- -Hydroxybutyrate by Brain in Diabetic Rats

Openshaw, Harry; Diamond, Ivan

doi:10.1001/archneur.1975.00490510096011

Archives of Neurology

1975

DOI: 10.1001/archneur.1975.00490510096011

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Extraction of D- -Hydroxybutyrate by Brain in Diabetic Rats

Harry Openshaw¹,

Ivan Diamond²

Abstract: Statistically significant cerebral arteriovenous differences of D-beta-hydroxybutyrate were found in rats made diabetic by administration of streptozotocin. The amount of D-beta-hydroxybutyrate extracted by the brain in diabetic animals increased with increasing arterial concentrations and the extraction ratios were comparable to those found in animals and humans with ketosis due to other causes.

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1976

1985

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Cited by 3 publications

References 14 publications

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Effects of diabetes, β-hydroxybutyric acid and metabolic acidosis on the pituitary-thyroid axis in the rat

Boado

Colombo

Zaninovich

1985

J Endocrinol Invest

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Previous studies demonstrated alterations of thyroidal economy in untreated diabetes mellitus both in man and experimental animals. To test the role of beta-hydroxybutyric acid (BHB) and acidosis in generating such changes, we studied the pituitary-thyroid axis of streptozotocin-diabetic rats, BHB or ammonium chloride (NH4Cl)-treated normal rats. Serum TSH, pituitary content and pituitary concentration of TSH, serum T4, T3 and free T4 (FT4), were all measured by RIA. In short term (2 days) diabetic rats the pituitary content of TSH was normal whereas the concentration (per mg of protein) was elevated (p less than 0.05 versus control group). Serum TSH (p less than 0.05), serum T4 (p less than 0.05), serum T3 (p less than 0.01) and serum FT4 (p less than 0.05) were all significantly decreased. In long term (30 days) untreated diabetic rats serum changes were similar to the short term diabetic group, though the pituitary content of TSH was significantly decreased (p less than 0.05). Animals treated with NH4Cl had no variations from controls. However, rats treated with BHB displayed a significant decrease in pituitary content of TSH (p less than 0.05), pituitary concentration of TSH (p less than 0.05) and in plasma TSH (p less than 0.01), and normal thyroid hormones in serum. No significant changes were seen in the TSH response to TRH in 2 or 30 days untreated diabetic and in BHB - treated animals. The data suggest that BHB, although not NH4Cl acidosis, may be capable of inducing a moderate depression of pituitary and plasma TSH of a lesser magnitude of that accompanying the full, long term diabetic state in the rat.

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Effects of diabetes, β-hydroxybutyric acid and metabolic acidosis on the pituitary-thyroid axis in the rat

Boado

Colombo

Zaninovich

1985

J Endocrinol Invest

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LEUCINE OXIDATION IN BRAIN SLICES AND NERVE ENDINGS¹

Chaplin¹,

Goldberg²,

Diamond³

1976

Journal of Neurochemistry

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—It is generally believed that leucine serves primarily as a precursor for protein synthesis in the central nervous system. However, leucine is also oxidized to CO2 in brain. The present investigation compares leucine oxidation and incorporation into protein in brain slices and synaptosomes. In brain slices from adult rats, these processes were linear for 90min and 14CO2 production from 0·1 mm‐l‐[l‐14C]leucine was 23 times more rapid than incorporation into protein. The rate of oxidation increased further with greater leucine concentrations. Experiments with l‐[U‐14C]leucine suggested that all of the carbons from leucine were oxidized to CO2 with very little incorporation into lipid. Oxidation of leucine also occurred in synaptosomes. In slices, leucine oxidation and incorporation into protein were inhibited by removal of glucose or Na+, or addition of ouabain. In synaptosomes, replacement of Na+ by choline also reduced leucine oxidation; and this effect did not appear to be due to inhibition of leucine transport. The rate of leucine oxidation did not change in brain slices prepared from fasted animals. Fasting, however, reduced the incorporation of leucine into protein in brain slices prepared from young but not from adult rats. These findings indicate that oxidation is the major metabolic fate of leucine in brain of fed and fasted animals.

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Transcription of Repeated and Unique Dna Sequences in Brain Nuclei

Chaplin¹,

Goldberg²,

Diamond

1976

Journal of Neurochemistry

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—Transcription of repeated and unique DNA in rat brain nuclei was examined using a RNA‐DNA hybridization technique. Saturation hybridization experiments with a membrane filter showed that there were differences in the base sequence complements between labelled brain and labelled liver nuclear RNA. In competition hybridization experiments using a membrane filter, brain nuclear labelled RNA was in competition most effectively with unlabelled brain nuclear RNA, but less effectively with kidney or liver nuclear RNA. Experiments using a membrane filter loaded with isolated unique or repeated DNA fragments gave similar results. Furthermore, competition hybridization with a DNA excess also showed similar results at Cot 10,000. These results indicate the existence of tissue‐specificity in the transcription of unique and repeated DNA sequences in brain nuclei. Subsequently, rat brain nuclei were separated into neuronal and glial nuclear fractions for the purpose of detecting the cell‐specificity of RNA. The results of these experiments give evidence of significant differences in the transcription of unique DNA sequences, but indicate no differences in that of repeated DNA sequences between the two nuclear classes.

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Extraction of D- -Hydroxybutyrate by Brain in Diabetic Rats

Cited by 3 publications

References 14 publications

Effects of diabetes, β-hydroxybutyric acid and metabolic acidosis on the pituitary-thyroid axis in the rat

Effects of diabetes, β-hydroxybutyric acid and metabolic acidosis on the pituitary-thyroid axis in the rat

LEUCINE OXIDATION IN BRAIN SLICES AND NERVE ENDINGS¹

Transcription of Repeated and Unique Dna Sequences in Brain Nuclei

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Product

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About

Extraction of D- -Hydroxybutyrate by Brain in Diabetic Rats

Cited by 3 publications

References 14 publications

Effects of diabetes, β-hydroxybutyric acid and metabolic acidosis on the pituitary-thyroid axis in the rat

Effects of diabetes, β-hydroxybutyric acid and metabolic acidosis on the pituitary-thyroid axis in the rat

LEUCINE OXIDATION IN BRAIN SLICES AND NERVE ENDINGS1

Transcription of Repeated and Unique Dna Sequences in Brain Nuclei

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LEUCINE OXIDATION IN BRAIN SLICES AND NERVE ENDINGS¹