The effect of hyperglycemia on extracellular levels of adenosine in the hypoxic rat cerebral cortex

Phillis, John W.; Simpson, Richard E.; Walter, Gary A.

doi:10.1016/0006-8993(90)90712-k

Cited by 13 publications

(4 citation statements)

References 18 publications

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“…In hyperglycaemic conditions, such as those that occur in diabetes, adenosine may play a role in regulating blood sugar levels. An increased glucose concentration was associated with decreased adenosine levels [ 42 , 43 ]. One way that adenosine may be involved in regulating blood sugar levels is through its effects on insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Profiling Reveals the Role of PEDF in Triple-Negative Breast Cancer Cell MDA-MB-231 under Glycaemic Loading

et al. 2023

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Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein that belongs to the serine protease inhibitor (serpin) family. An increase in PEDF activity has been shown to be a potent inhibitor of tumour progression and proliferation, suggesting a possible therapeutic target. There is still a great deal to learn about how PEDF controls metabolic pathways in breast cancer and its metastatic form. Given this, the primary purpose of this study was to use a metabolomics approach to gain a better understanding of the mechanisms driving the reprogramming of metabolic events involved in breast cancer pertaining to PEDF under various glycaemic loads. We employed gas chromatography–quadrupole mass spectrometry (GC-Q-MS) to investigate metabolic changes in the triple-negative breast cancer (TNBC) cell line MDA-MB-231 treated with PEDF under glycaemic loading. Multivariate and univariate analyses were carried out as indicative tools via MetaboAnalyst (V.5.0) and R packages to identify the significantly altered metabolites in the MDA-MB-231 cell line after PEDF exposure under glycaemic loading. A total of 61 metabolites were found, of which nine were selected to be distinctively expressed in MDA-MB-231 cells under glycaemic conditions and exhibited differential responses to PEDF (p < 0.05, VIP > 1). Abnormalities in amino acid metabolism pathways were observed. In particular, glutamic acid, glutamine, and phenylalanine showed different levels of expression across different treatment groups. The lactate and glucose-6-phosphate production significantly increased in high-glucose vs. normal conditions while it decreased when the cells were exposed to PEDF, confirming the positive influence on the Warburg effect. The TCA cycle intermediates, including malate and citric acid, showed different patterns of expression. This is an important finding in understanding the link of PEDF with metabolic perturbation in TNBC cells in response to glycaemic conditions. Our findings suggest that PEDF significantly influenced the Warburg effect (as evidenced by the significantly lower levels of lactate), one of the well-known metabolic reprogramming pathways in cancer cells that may be responsive to metabolic-targeted therapeutic strategies. Moreover, our results demonstrated that GC-MS-based metabolomics is an effective tool for identifying metabolic changes in breast cancer cells after glycaemic stress or in response to PEDF treatment.

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Section: Discussionmentioning

confidence: 99%

Metabolomics Profiling Reveals the Role of PEDF in Triple-Negative Breast Cancer Cell MDA-MB-231 under Glycaemic Loading

et al. 2023

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“…Neonate brain and brain slices may be less susceptible to glycemic state because they do not tend to accumulate lactate during hypoxia Hatton and Wasterlain, 1990). In contrast, hyperglycemia in adult animals results in an accumulation of lactate and a diminished output of the normally cerebroprotective adenosine (Plum, 1983;Phillis et al, 1990;Hsu et al, 1991). The present results indicate an interaction between lactate and adenosine such that an increase in lactate may contribute to a decline in adenosine production.…”

Section: Discussionmentioning

confidence: 99%

Glucose Deprivation Results in a Lactate Preventable Increase in Adenosine and Depression of Synaptic Transmission in Rat Hippocampal Slices

Fowler

1993

Journal of Neurochemistry

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: The effect of glucose deprivation on adenosine levels and on synaptic transmission was investigated in rat hippocampal slices. Incubation of hippocampal slices either in glucose‐free medium or in the presence of the glucose transport inhibitor cytochalasin B (50 μM) increased bath adenosine levels and depressed the extracellularly recorded synaptic potential or population spike. The addition of lactate (10 mM), a precursor for mitochondrial ATP generation, prevented the elevation in adenosine and the depression of the population spike. These results indicate that the neuroinhibitory modulator adenosine is elevated during glucose deprivation and contributes to the hypoglycemic depression of synaptic transmission. The increase in adenosine during glucose deprivation can be prevented by providing substrate for mitochondrial ATP generation. The present results indicate an interaction between lactate and adenosine such that an increase in lactate may contribute to a decline in adenosine production.

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“…For example, rocking, spinning and Grandin's “hug machine” [13] exert mechanical pressure or induce sudden changes in acceleration, and thus may exert their effects through increased extracellular adenosine, similar to local increases via impact or acupuncture [19, 21]. Conversely, basic research indicates that hyperglycemia and increased pH each could decrease adenosine acutely [8, 9, 40]. Because adenosine is uniquely poised to link metabolism and brain activity, we speculate that some behaviors which increase adenosine could represent metabolic reinforcement - a form of self-medication by attempting to self-regulate neuronal excitability through increased adenosine.…”

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confidence: 99%

The relationship between the neuromodulator adenosine and behavioral symptoms of autism

Masino

Kawamura

Plotkin

et al. 2011

Neuroscience Letters

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The neuromodulator adenosine is an endogenous sleep promoter, neuroprotector and anticonvulsant, and people with autism often suffer from sleep disruption and/or seizures. We hypothesized that increasing adenosine can decrease behavioral symptoms of autism, and, based on published research, specific physiological stimuli are expected to increase brain adenosine. To test the relationship between adenosine and autism, we developed a customized parent-based questionnaire to assess child participation in activities expected to influence adenosine and quantify behavioral changes following these experiences. Parents were naive to study hypotheses and all conditions were pre-assigned. Results demonstrate significantly better behavior associated with events pre-established as predicted to increase rather than decrease or have no influence on adenosine. Understanding the physiological relationship between adenosine and autism could open new therapeutic strategies - potentially preventing seizures, improving sleep, and reducing social and behavioral dysfunction.

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The effect of hyperglycemia on extracellular levels of adenosine in the hypoxic rat cerebral cortex

Cited by 13 publications

References 18 publications

Metabolomics Profiling Reveals the Role of PEDF in Triple-Negative Breast Cancer Cell MDA-MB-231 under Glycaemic Loading

Metabolomics Profiling Reveals the Role of PEDF in Triple-Negative Breast Cancer Cell MDA-MB-231 under Glycaemic Loading

Glucose Deprivation Results in a Lactate Preventable Increase in Adenosine and Depression of Synaptic Transmission in Rat Hippocampal Slices

The relationship between the neuromodulator adenosine and behavioral symptoms of autism

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