The Effect of Insulin Infusion on the Metabolites in Cerebral Tissues Assessed With Proton Magnetic Resonance Spectroscopy in Young Healthy Subjects With High and Low Insulin Sensitivity

Karczewska-Kupczewska, Monika; Tarasów, Eugeniusz; Nikołajuk, Agnieszka; Stefanowicz, Magdalena; Matulewicz, Natalia; Otziomek, Elżbieta; Górska, Maria; Strączkowski, Marek; Kowalska, Irina

doi:10.2337/dc12-1437

Cited by 28 publications

(25 citation statements)

References 40 publications

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“…Genetic profiles and cultural and environmental factors should also be considered in interpreting the results. However, these results are, to some extent, in accordance with those of a previous report on the role of insulin in controlling the neuronal survival while mediating the gene expression in the brain (11) and with those of a study on the lower prefrontal NAA levels in T2DM (3), which included other ethnic groups.…”

Section: Discussionsupporting

confidence: 92%

Obesity May Connect Insulin Resistance to Decreased Neuronal Viability in Human Diabetic Brain

Lee

Joo

Kim

et al. 2020

Obesity

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Objective This study aimed to investigate the relationship between insulin resistance and markers of neuronal viability and energy metabolism, as well as the additive effects of overweight or obesity, in individuals with type 2 diabetes mellitus (T2DM). Methods Using 1H‐magnetic resonance spectroscopy, prefrontal N‐acetyl aspartate (NAA) and creatine levels, markers for neuronal viability and energy metabolism, respectively, were measured in 50 adults with overweight or obesity and T2DM (T2DM‐O; aged 49.0 ± 7.4 years; 50% female), 50 adults with normal weight and T2DM (T2DM‐N), and 50 healthy adults with normal weight (healthy‐control [HC] group) matched for age and sex. The homeostatic model assessment for insulin resistance levels were calculated to assess insulin resistance. Results Prefrontal NAA levels were lower in the T2DM‐O group relative to the HC group (t = −2.51, P = 0.013). Higher insulin resistance was associated with lower prefrontal NAA levels in the T2DM‐O group (t = −2.21, P = 0.032) but not in the T2DM‐N group (t = −0.72, P = 0.48). Prefrontal creatine levels did not differ across the three groups. Conclusions Overweight and obesity might contribute to T2DM‐related neuronal viability deficits and could be the key links that connect insulin resistance to the decreased neuronal viability in the human diabetic brain.

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Section: Discussionsupporting

confidence: 92%

Obesity May Connect Insulin Resistance to Decreased Neuronal Viability in Human Diabetic Brain

Lee

Joo

Kim

et al. 2020

Obesity

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“…Nonobese type 2 diabetic Goto-Kakizaki rats show decreased mRNA transcript levels of the pineal insulin receptors [43] and have lower serotonin and tryptophan levels in the pineal gland, which is part of the epithalamus [44]. Furthermore, a lower increase in glucose levels within the thalamus was found in response to plasma hyperglycemia in type 1 diabetic humans compared to nondiabetic humans [45], suggesting a role for circulating insulin, although frontal and temporal cerebral metabolites, measured using spectroscopy, were not different under hyperinsulinemic conditions in the thalamus between lean men with high versus low insulin sensitivity [46]. The currently used imaging tool does not have the spatial resolution to evaluate SERT binding in such small brain areas, and translational research in rodents is needed to study this in more detail.…”

Section: Discussionmentioning

confidence: 99%

Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans

Versteeg

Koopman²,

Booij

et al. 2016

Neuroendocrinology

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Background: Altered brain dopaminergic and serotonergic pathways have been shown in obese rodents and humans, but it is unknown whether this is related to obesity per se or to the metabolic derangements associated with obesity. Methods: We performed a case-control study in insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) subjects (n = 12) and age-matched lean controls (n = 8) and measured serotonin transporter (SERT) binding in the whole diencephalon and specifically in the hypothalamus, as well as dopamine transporter (DAT) binding in the striatum using ¹²³I- FP-CIT single-photon emission computed tomography. We assessed insulin sensitivity using the homeostatic model assessment of insulin resistance. Results: BMI did not differ between the IRO and ISO subjects. SERT binding in the diencephalon was significantly lower in IRO than in ISO subjects, but was not different between lean and obese subjects. SERT binding in the hypothalamus tended to be reduced in obese versus lean subjects, but was not different between IRO and ISO subjects. Striatal DAT binding was similar between lean and obese subjects as well as between ISO and IRO subjects. Conclusions: We conclude that SERT binding in the diencephalon is reduced in insulin-resistant subjects independently of body weight, while hypothalamic SERT binding tends to be lower in obesity, with no difference between insulin-resistant and insulin-sensitive subjects. This suggests that the metabolic perturbations associated with obesity independently affect SERT binding within the diencephalon.

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“…We did not detect significant group differences in GFAP protein levels in either the hippocampus or the striatum, however. Moreover, we did not detect significant differences in mIns, a glial cell marker, or NAA, a marker of neural health [20,33]. It is tempting to attribute lack of glial activation to a potential compensatory upregulation of NAAG, since NAAG is neuroprotective against increased glutamate activity [34,35].…”

Section: Discussionmentioning

confidence: 99%

A high fat diet alters metabolic and bioenergetic function in the brain: A magnetic resonance spectroscopy study

Raider

Harris

et al. 2016

Neurochemistry International

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Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy (1H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs. normal low fat chow. We detected lower concentrations of total creatine (tCr) and a lower glutamate-to-glutamine ratio in the hippocampus of high fat rats. Additional effects observed in the hippocampus of high fat rats included higher N-acetylaspartylglutamic acid (NAAG), and lower myo-inositol (mIns) and serine (Ser) concentrations. Post-mortem tissue analyses revealed lower phosphorylated AMP-activated protein kinase (pAMPK) in the striatum but not in the hippocampus of high fat rats. Hippocampal pAMPK levels correlated significantly with tCr, aspartate (Asp), phosphoethanolamine (PE), and taurine (Tau), indicating beneficial effects of AMPK activation on brain metabolic and energetic function, membrane turnover, and edema. A negative correlation between pAMPK and glucose (Glc) indicates a detrimental effect of brain Glc on cellular energy response. Overall, these changes indicate alterations in neurotransmission and in metabolic and bioenergetic function in the hippocampus and in the striatum of rats fed a high fat diet.

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The Effect of Insulin Infusion on the Metabolites in Cerebral Tissues Assessed With Proton Magnetic Resonance Spectroscopy in Young Healthy Subjects With High and Low Insulin Sensitivity

Cited by 28 publications

References 40 publications

Obesity May Connect Insulin Resistance to Decreased Neuronal Viability in Human Diabetic Brain

Obesity May Connect Insulin Resistance to Decreased Neuronal Viability in Human Diabetic Brain

Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans

A high fat diet alters metabolic and bioenergetic function in the brain: A magnetic resonance spectroscopy study

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