Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients

2002 ◽  
Vol 283 (1) ◽  
pp. E20-E28 ◽  
Author(s):  
G. Blomqvist ◽  
M. Alvarsson ◽  
V. Grill ◽  
G. Von Heijne ◽  
M. Ingvar ◽  
...  
Keyword(s):  
Time Course ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Tissue Concentration ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Utilization Rate ◽  
Resonance Spectroscopy ◽  
Significant Difference ◽  
The Brain

Using R-β-[1-11C]hydroxybutyrate and positron emission tomography, we studied the effect of acute hyperketonemia (range 0.7–1.7 μmol/ml) on cerebral ketone body utilization in six nondiabetic subjects and six insulin-dependent diabetes mellitus (IDDM) patients with average metabolic control (HbA1c = 8.1 ± 1.7%). An infusion of unlabeled R-β-hydroxybutyrate was started 1 h before the bolus injection of R-β-[1-11C]hydroxybutyrate. The time course of the radioactivity in the brain was measured during 10 min. For both groups, the utilization rate of ketone bodies was found to increase nearly proportionally with the plasma concentration of ketone bodies (1.0 ± 0.3 μmol/ml for nondiabetic subjects and 1.3 ± 0.3 μmol/ml for IDDM patients). No transport of ketone bodies from the brain could be detected. This result, together with a recent study of the tissue concentration of R-β-hydroxybutyrate in the brain by magnetic resonance spectroscopy, indicate that, also at acute hyperketonemia, the rate-limiting step for ketone body utilization is the transport into the brain. No significant difference in transport and utilization of ketone bodies could be detected between the nondiabetic subjects and the IDDM patients.

Use of R-beta-[1-11C]hydroxybutyrate in PET studies of regional cerebral uptake of ketone bodies in humans

1995 ◽  
Vol 269 (5) ◽  
pp. E948-E959 ◽  
Author(s):  
G. Blomqvist ◽  
J. O. Thorell ◽  
M. Ingvar ◽  
V. Grill ◽  
L. Widen ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Animal Studies ◽  
Time Course ◽  
Ketone Bodies ◽  
Tracer Uptake ◽  
Utilization Rate ◽  
Rate Limiting Step ◽  
Positron Emission ◽  
Beta Hydroxybutyrate ◽  
The Brain

A method for determining regional cerebral utilization of ketone bodies in humans is described. After a bolus injection of R-beta-[1-11C]hydroxybutyrate, the time course of the tracer in the brain was measured with positron emission tomography in five healthy volunteers. The regional cerebral blood flow was measured separately. The tracer uptake in the brain could be well described by a single rate constant, indicating that the concentration of unmetabolized ketone bodies in the brain is very low and that transport across the blood-brain barrier is the rate-limiting step. At an average plasma concentration of beta-hydroxybutyrate of 0.043 mumol/ml, the utilization rate was estimated to be 0.48 nmol.ml-1.min-1. In accordance with previous animal studies, the utilization rate was found to increase almost linearly with increasing plasma concentration of beta-hydroxybutyrate. Furthermore, the utilization was higher in gray than in white matter. Finally, the ratio between the utilization in the basal ganglia and the brain as a whole was lower for ketone bodies than for glucose.

scholarly journals Ketone body 3-hydroxybutyrate as a biomarker of aggression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. M. Whipp ◽  
E. Vuoksimaa ◽  
T. Korhonen ◽  
R. Pool ◽  
A. But ◽  
...  
Keyword(s):  
Young Adults ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Population Based ◽  
Resonance Spectroscopy ◽  
Linear Regression Models ◽  
Complex Behaviour ◽  
Replication Sample ◽  
Discovery Sample ◽  
Independent Replication

AbstractHuman aggression is a complex behaviour, the biological underpinnings of which remain poorly known. To gain insights into aggression biology, we studied relationships with aggression of 11 low-molecular-weight metabolites (amino acids, ketone bodies), processed using 1H nuclear magnetic resonance spectroscopy. We used a discovery sample of young adults and an independent adult replication sample. We studied 725 young adults from a population-based Finnish twin cohort born 1983–1987, with aggression levels rated in adolescence (ages 12, 14, 17) by multiple raters and blood plasma samples at age 22. Linear regression models specified metabolites as the response variable and aggression ratings as predictor variables, and included several potential confounders. All metabolites showed low correlations with aggression, with only one—3-hydroxybutyrate, a ketone body produced during fasting—showing significant (negative) associations with aggression. Effect sizes for different raters were generally similar in magnitude, while teacher-rated (age 12) and self-rated (age 14) aggression were both significant predictors of 3-hydroxybutyrate in multi-rater models. In an independent replication sample of 960 adults from the Netherlands Twin Register, higher aggression (self-rated) was also related to lower levels of 3-hydroxybutyrate. These exploratory epidemiologic results warrant further studies on the role of ketone metabolism in aggression.

scholarly journals Cortical Substrate Oxidation during Hyperketonemia in the Fasted Anesthetized Rat in Vivo

2011 ◽  
Vol 31 (12) ◽  
pp. 2313-2323 ◽  
Author(s):  
Lihong Jiang ◽  
Graeme F Mason ◽  
Douglas L Rothman ◽  
Robin A de Graaf ◽  
Kevin L Behar
Keyword(s):  
Time Course ◽  
Ketone Bodies ◽  
Tricarboxylic Acid Cycle ◽  
Metabolic Model ◽  
Substrate Oxidation ◽  
Resonance Spectroscopy ◽  
Neural Function ◽  
Anesthetized Rats ◽  
Time Courses

Ketone bodies are important alternate brain fuels, but their capacity to replace glucose and support neural function is unclear. In this study, the contributions of ketone bodies and glucose to cerebral cortical metabolism were measured in vivo in halothane-anesthetized rats fasted for 36 hours ( n=6) and receiving intravenous [2,4-13C2]-d- β-hydroxybutyrate (BHB). Time courses of 13C-enriched brain amino acids (glutamate-C4, glutamine-C4, and glutamate and glutamine-C3) were measured at 9.4 Tesla using spatially localized 1H-[13C]-nuclear magnetic resonance spectroscopy. Metabolic rates were estimated by fitting a constrained, two-compartment (neuron–astrocyte) metabolic model to the 13C time-course data. We found that ketone body oxidation was substantial, accounting for 40% of total substrate oxidation (glucose plus ketone bodies) by neurons and astrocytes. d- β-Hydroxybutyrate was oxidized to a greater extent in neurons than in astrocytes (∼70:30), and followed a pattern closely similar to the metabolism of [1-13C]glucose reported in previous studies. Total neuronal tricarboxylic acid cycle (TCA) flux in hyperketonemic rats was similar to values reported for normal (nonketotic) anesthetized rats infused with [1-13C]glucose, but neuronal glucose oxidation was 40% to 50% lower, indicating that ketone bodies had compensated for the reduction in glucose use.

scholarly journals Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats

1974 ◽  
Vol 138 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Neil B. Ruderman ◽  
Peter S. Ross ◽  
Michael Berger ◽  
Michael N. Goodman
Keyword(s):  
Glucose Uptake ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Acetyl Coa ◽  
Total Blood ◽  
Diabetic Ketosis ◽  
Pyruvate Oxidation ◽  
Ketone Body Metabolism ◽  
Arteriovenous Difference ◽  
The Brain

1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O2 consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain 's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the accelerated rate of ketone-body metabolism; however, we found no correlation between the decrease in glucose uptake in the diabetic state and the arteriovenous difference for ketone bodies. 12. The data also suggest that the rates of acetoacetate and 3-hydroxybutyrate utilization by brain are governed by their concentrations in plasma. 13. The finding of very low concentrations of acetoacetate and 3-hydroxybutyrate in brain compared with plasma suggests that diffusion across the blood –brain barrier may be the rate-limiting step in their metabolism.

scholarly journals Ketone body 3-hydroxybutyrate: a biomarker of aggression?

2020 ◽  
Author(s):  
alyce m whipp ◽  
eero vuoksimaa ◽  
tellervo korhonen ◽  
rene pool ◽  
lannie ligthart ◽  
...  
Keyword(s):  
Young Adults ◽  
Fixed Effects ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Population Based ◽  
Resonance Spectroscopy ◽  
Linear Regression Models ◽  
Replication Sample ◽  
Discovery Sample ◽  
Independent Replication

Human aggression is a complex behavior, the biological underpinnings of which remain poorly known. To gain insights into aggression biology, we studied relationships with aggression of 11 low-molecular-weight metabolites (amino acids, ketone bodies), processed using 1H nuclear magnetic resonance spectroscopy. We used a discovery sample of young adults and an independent adult replication sample. We studied 725 young adults from a population-based Finnish twin cohort born 1983-87, with aggression levels rated in adolescence (ages 12, 14, 17) by multiple raters and blood plasma samples at age 22. Linear regression models specified metabolites as the dependent and aggression ratings as independent variables, and included several fixed effects. All metabolites showed low correlations with aggression, with only one - 3-hydroxybutyrate, a ketone body produced during fasting - showing significant (negative) associations with aggression. Effect sizes for different raters were generally similar in magnitude, while teacher-rated (age 12) and self-rated aggression (age 14) were both significant predictors of 3-hydroxybutyrate in multi-rater models. In an independent replication sample of 960 adults from the Netherlands Twin Register, higher self-rated aggression was also related to lower levels of 3-hydroxybutyrate. These exploratory epidemiologic results warrant further studies on the role of ketone metabolism in aggression.

scholarly journals SARS-CoV-2 Infection Related Diabetes Mellitus

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A397-A397
Author(s):  
Kara A Beliard ◽  
Mabel Yau ◽  
Meredith Wilkes ◽  
Christopher Joseph Romero ◽  
Elizabeth Wallach ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Case Report ◽  
Pancreatic Beta Cells ◽  
Time Course ◽  
Insulin Dependent Diabetes Mellitus ◽  
Islet Autoimmunity ◽  
Total Daily Dose ◽  
Dependent Diabetes Mellitus ◽  
Pcr Analysis ◽  
Family History Of Diabetes

Abstract Introduction: SARS-Cov-2 (severe acute respiratory distress syndrome- coronavirus 2) viral infection has a predilection for pancreatic beta cells causing insulin deficiency. Studies from the SARS-CoV outbreak in 2003 highlighted the relationship between SARS-CoV and ACE-2 (angiotensin-converting enzyme 2) receptors in pancreatic islet cells. We describe a pediatric patient who developed Diabetes Mellitus after exposure to the Sars-CoV-2 virus. Case Report: A previously healthy 13-year-old female of Mexican descent was found to be hyperglycemic at her annual visit. The patient endorsed polyuria and polydipsia for 3 weeks, and weight loss for 3months. 3 months prior to presentation, her mother became ill and tested positive for SARS-CoV-2 by PCR analysis. The patient had no SARS-CoV-2 associated symptoms. Her exam was notable for a BMI was in the 78%ile for age with no acanthosis nigricans. She had no family history of diabetes or autoimmune disease. Initial blood glucose was 729 mg/dL, with bicarbonate of 20.6 mEq/L, pH 7.45, and anion gap of 14 mEq/L. Large ketones were present in the urine. Her concomitant C-peptide level of 1.0 ng/ml was low in the setting of hyperglycemia. Her HbA1c was 14.3%. Diabetes-related autoantibodies, celiac, and thyroid antibodies were negative. Her Sars-CoV-2 antibody titer was positive with a negative PCR. The patient was treated with a basal-bolus regimen of subcutaneous insulin at a maximal total daily dose of 0.7 u/kg/day. 5 weeks later, her insulin requirement and HbA1C were both lower; at 0.5 u/kg/day and 9.3% respectively. Discussion: This patient’s symptoms of hyperglycemia started shortly after her exposure to the SARS-CoV-2 virus. She had no features consistent with Type 2 DM. She similarly had no serological evidence of DM related autoimmunity, thus being different from reports of new-onset Type 1 DM with confirmed autoimmunity presenting during the Sars-CoV-2 pandemic. Although Type 1B DM without evidence of humoral islet autoimmunity and monogenic DM could not be fully excluded, we postulate that the patient developed SARS-CoV-2 associated DM given her time course and documented exposure to SARS –CoV-2 with the presence of SARS-CoV antibodies. One similar case has previously been reported By Holstein et al. 1 While we share the lack of direct evidence of causation, we postulate that more patients with similar presentations will be reported during the current pandemic. Reference: 1.Hollstein, T et al. Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report [published online ahead of print, 2020 Sep 2]. Nat Metab. 2020;10.1038/s42255-020-00281-8. doi:10.1038/s42255-020-00281-8

scholarly journals Analysis of Mental State of Patients after Drug Addiction and Withdrawal Guided by PETCT Image Based on Optimized Image Fusion Algorithm

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yaowen Pang ◽  
Xiang Peng
Keyword(s):  
Prefrontal Cortex ◽  
Magnetic Resonance ◽  
Visual Stimulation ◽  
Brain Temperature ◽  
Statistical Significance ◽  
Normal Group ◽  
Resonance Spectroscopy ◽  
Significant Difference ◽  
Before And After ◽  
The Brain

Blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) studies have shown that drug-dependent patients are activated in different addictive brain areas under the stimulation of relevant environmental cues, which in turn leads to craving and relapse. This study uses magnetic resonance spectroscopy to measure brain temperature to explore the brain temperature changes in different addictive brain regions of heroin and methamphetamine addicts in a short-term withdrawal state and to explore whether the quantitative index of brain temperature change can be used as a diagnostic drug Methods. The subjects were scanned by resting-state MRI spectroscopy first and then subjected to MRI spectroscopy scanning under visual stimulation. The subjects were required to watch the heroin/meth-related clue pictures carefully during visual stimulation. The measured chemical shift value of N-acetyl-aspartic acid (NAA) is substituted into the brain temperature calculation formula T = 37 + 100 to obtain the brain temperature before and after visual stimulation. In addition, the anxiety and depression states of heroin and methamphetamine-dependent patients were evaluated. Results. There was no statistically significant change in the brain temperature of the prefrontal cortex before and after visual stimulation in heroin and methamphetamine-dependent subjects; compared with the normal group, there was no change in prefrontal cortex brain temperature before and after visual stimulation in heroin and methamphetamine-dependent subjects. Statistical Significance. The changes of hippocampal temperature before and after visual stimulation in methamphetamine-dependent patients were not statistically significant; compared with the normal group, there was no statistically significant difference in the changes of hippocampal temperature before and after visual stimulation in methamphetamine-dependent patients. Conclusion. This study initially found that the visual cues related to heroin and methamphetamine were not enough to cause significant changes in the brain temperature of the prefrontal cortex.

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