The Pentose Phosphate Pathway in Skeletal Muscle Under Patho-Physiological Conditions

Meijer, A. E. F. H.

doi:10.1016/s0079-6336(11)80052-5

Cited by 15 publications

(15 citation statements)

References 297 publications

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“…In agreement with recent studies from Kahn and colleagues, who used an HFD for 8 weeks (39), we observed increases in muscle glucose and glucose-6-phosphate content after an HFD at the basal level. Interestingly, we observed activation of the pentose phosphate pathway by HFD, although this pathway is typically not active in muscle cells and only observed in cases such as tissue damage or disease (42). Together, these data suggest that improved mitochondrial function may be another underlying mechanism via which adiponectin exerts its insulin-sensitizing effect.…”

Section: Discussionmentioning

confidence: 88%

Adiponectin Corrects High-Fat Diet–Induced Disturbances in Muscle Metabolomic Profile and Whole-Body Glucose Homeostasis

et al. 2013

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We provide here a detailed and comprehensive analysis of skeletal muscle metabolomic profiles in response to adiponectin in adiponectin knockout (AdKO) mice after high-fat–diet (HFD) feeding. Hyperinsulinemic-euglycemic clamp studies showed that adiponectin administration corrected HFD-induced defects in post/basal insulin stimulated Rd and insulin signaling in skeletal muscle. Lipidomic profiling of skeletal muscle from HFD-fed mice indicated elevated triacylglycerol and diacylglycerol species (16:0–18:1, 18:1, and 18:0–18:2) as well as acetyl coA, all of which were mitigated by adiponectin. HFD induced elevated levels of various ceramides, but these were not significantly altered by adiponectin. Adiponectin corrected the altered branched-chain amino acid metabolism caused by HFD and corrected increases across a range of glycerolipids, fatty acids, and various lysolipids. Adiponectin also reversed induction of the pentose phosphate pathway by HFD. Analysis of muscle mitochondrial structure indicated that adiponectin treatment corrected HFD-induced pathological changes. In summary, we show an unbiased comprehensive metabolomic profile of skeletal muscle from AdKO mice subjected to HFD with or without adiponectin and relate these to changes in whole-body glucose handling, insulin signaling, and mitochondrial structure and function. Our data revealed a key signature of relatively normalized muscle metabolism across multiple metabolic pathways with adiponectin supplementation under the HFD condition.

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Section: Discussionmentioning

confidence: 88%

Adiponectin Corrects High-Fat Diet–Induced Disturbances in Muscle Metabolomic Profile and Whole-Body Glucose Homeostasis

et al. 2013

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“…As the PPP is the main source of defense against oxidative stress in neurons, we thought it important to characterize the usage of this pathway in PD. Studies showing increased activity of the PPP in AD (Martins et al., 1986), neuromuscular diseases (Meijer, 1991), myocardial infarction (Gupte, 2008), and studies using hepatocyte cell models (Ursini et al., 1997) support the idea that oxidative stress is normally met with increased production of NADPH. However, characterization of the PPP in our experiments has shown that NADPH production is not increased in the putamen of samples with early stage PD and furthermore, PPP enzyme levels are actually decreased.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

Dunn¹,

Allen

Mamais³

et al. 2014

Neurobiology of Aging

192

136

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Unlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD.

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“…Free radicals, such as superoxide anions, play a fundamental role in many pathological conditions connected with DNA damage, enzyme destruction, lipid peroxidation and rupture of cell and lysosomal membranes, but can be important also in physiological situations, such as regression, degeneration and aging processes (for reviews, see Simic et al, 1988;Haliwell & Gutteridge, 1989;Meijer, 1991). Cell organelles are vulnerable to the action of these free radicals, and thus enhanced generation of oxyradicals in the decidua may lead to increased lysosomal permeability and leakage of hydrolytic enzymes.…”

Section: Discussionmentioning

confidence: 99%

Comparative enzyme histochemistry of the early and term rat decidua with special attention to decidual regression

Straatsburg

Gossrau

1994

Histochem J

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As the early rat decidua is believed to fulfil functions other than the late or basal decidua, the question as to whether this difference is reflected in decidual cell metabolism was investigated. Using cryosections of pregnant rat uteri of the 10th, 15th and 21st gestational day, activities of oxyradical-forming enzymes and hydrolases were analysed histochemically. The enzyme activities of decidual stromal cells and fibroblasts of the metrial gland exhibited three main fluctuations. One group of enzyme activities did not change during gestation, a second group decreased or disappeared, and a third group increased or was expressed in the late decidua only. Enzymes of the purine and polyamine pathway, including oxyradical-forming oxidases, were absent from early mesometrial decidual cells, but were highly active in the late regressing decidua and metrial gland. Some acid hydrolases and neutral proteases became active in the mature decidua. The possibility that purine-degrading and oxyradical-forming enzymes support decidual as well as metrial gland regression, and thus placental separation, by direct tissue damage and/or by indirect rupture of lysosomal membranes, inducing the release of acid hydrolases, is considered.

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The Pentose Phosphate Pathway in Skeletal Muscle Under Patho-Physiological Conditions

Cited by 15 publications

References 297 publications

Adiponectin Corrects High-Fat Diet–Induced Disturbances in Muscle Metabolomic Profile and Whole-Body Glucose Homeostasis

Adiponectin Corrects High-Fat Diet–Induced Disturbances in Muscle Metabolomic Profile and Whole-Body Glucose Homeostasis

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

Comparative enzyme histochemistry of the early and term rat decidua with special attention to decidual regression

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