The Impact of Inflammation on Pancreatic β-Cell Metabolism, Function and Failure in T1DM and T2DM: Commonalities and Differences

Newsholme, Philip; Keane, Kevin N.; Bittencourt, P. de; Krause, Maurício

doi:10.5772/55349

Cited by 2 publications

(5 citation statements)

References 154 publications

(282 reference statements)

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“…Along with that, all these groups also presented a decrease in the production of malate. Malate is an important component of mitochondrial metabolism [65,66]. The lower MMP and malate levels found in the groups of spermatozoa treated in the presence of H 2 O 2 suggest a decline in mitochondrial activity, which can also be related to loss of motility in those groups.…”

Section: Discussionmentioning

confidence: 99%

“…In the cytosol, malate dehydrogenase (MDH) reduces oxaloacetate (OAA) to malate, through oxidation of NADH to NAD + , which then enters in mitochondria. Once in mitochondria, the reverse reaction is performed by MDH, mediating the regeneration of NADH [65,66]. Herein, malate is a metabolite that plays a crucial role in mitochondrial respiration, being part of the TCA cycle and participating in the restoration of mitochondrial NADH levels [67,68].…”

Section: Discussionmentioning

confidence: 99%

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Hyperoside Supplementation in Preservation Media Surpasses Vitamin C Protection Against Oxidative Stress-Induced Damages in Human Spermatozoa.

Moreira

Pereira

Guerra-Carvalho

et al. 2021

Cell Physiol Biochem

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BACKGROUND/AIMS: Oxidative Stress (OS) is reported as one of the main causes of male infertility. Infertile couples often resort to assisted reproductive technology (ART) to achieve parenthood. However, preparation for ART protocols increases the exposer of gametes to OS. Thus, it is crucial to find suitable preservation media that can counteract the OS-induced damages in spermatozoa. In this work, we tested and compared the efficiency of vitamin C (VC) and hyperoside (HYP) as potential antioxidant supplements for sperm preservation media. METHODS: We evaluated the cytotoxicity of HYP (0, 5, 50, 100, and 500 µM) in spermatozoa. After incubation of sperm cells with VC (600 µM) and HYP (100 and 500 µM), in the presence and absence of H2O2 (300 µM), the following parameters were assessed: total sperm motility and vitality, OS biomarkers expression, total antioxidant capacity (TAC) of the media, percentage of DNA fragmentation, mitochondrial membrane potential (MMP), and metabolite quantification of the media by proton nuclear magnetic resonance (1H-NMR). RESULTS: The supplementation with VC (600 µM) and HYP (100 and 500 µM) did not induce any deleterious effects to the physiology and metabolism of the spermatozoa, after 1-hour of treatment. In the presence of H2O2 (300 µM), both VC and HYP were able to prevent some of the deleterious effects of H2O2 in sperm, which were represented by an increase in sperm motility, a decrease in DNA fragmentation, and a decreasing trend in lipid peroxidation levels. However, these antioxidants were not able to prevent the decrease of MMP associated with H2O2 treatment, nor were able to prevent the conversion of pyruvate into acetate (a reaction promoted by H2O2). CONCLUSION: The supplementation of sperm preservation media with VC and HYP could be beneficial for the preservation of sperm physiology. From the antioxidant conditions tested, the supplementation of media with HYP (100 µM) demonstrated the best results regarding sperm preservation, evidencing the higher antioxidant capacity of HYP compared to VC. Nevertheless, none of the antioxidants used was able to prevent the metabolic alterations promoted by H2O2 in spermatozoa.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hyperoside Supplementation in Preservation Media Surpasses Vitamin C Protection Against Oxidative Stress-Induced Damages in Human Spermatozoa.

Moreira

Pereira

Guerra-Carvalho

et al. 2021

Cell Physiol Biochem

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“…Glutamine also influences the expression of a number of genes related to cell protection and survival [215]. Importantly, glutamine is the immediate precursor of the glutamate moiety for glutathione (GSH = γ-glutamyl-cysteinylglycine), the main soluble antioxidant species within the cell, this being demonstrated in a number of cell types and tissues [208,[212][213][214][215][216][217][218][219]. Inasmuch as redox imbalances are characteristic of degenerative disorders [140,148] and aggregative diseases [141-143, 153, 154], glutamine status becomes of importance in dictating a healthy condition.…”

Section: Glutamine Metabolism and Its Importance For The Heat Shock Rmentioning

confidence: 99%

“…Thence, glutaminemediated increased fluxes through HBP may, on the one hand, block GSK-3β, thus liberating glycogen synthesis by glycogen synthase and, on the other, may liberate HSF1 thus allowing enhanced expression of HSP70 [55,238]. HBP is a nutrient-sensing pathway [226] that presents multiple connections with energy metabolism, not only with glycogen synthesis [219]. AMPK, which occupies a central position in metabolic regulation in order to avoid inflammatory dysregulation, phosphorylates and inhibits GFAT1, the flux-generating step of HBP, thus allowing for the downregulation of such a shunt from the glycolysis under low glucose situations [239].…”

Section: Glutamine Metabolism and Its Importance For The Heat Shock Rmentioning

confidence: 99%

“…Therefore, in high-glucose states, HBP may act adversely as GFAT1 gene expression is enhanced by hyperglycemia contributing to an exaggerated flux through HBP that can be deleterious [52]. Indeed, exacerbated HBP activity does contribute to insulin resistance rather than being cytoprotective [219]. In fact, overenhanced flux through HBP is an inducer of ER stress, while being associated with insulin resistance [52,241], obesity [242], and abnormal glucose disposal rate in T1DM [243] and T2DM itself [241].…”

Section: Glutamine Metabolism and Its Importance For The Heat Shock Rmentioning

confidence: 99%

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Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

Leite

Cruzat

Krause

et al. 2016

Nutrire

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Aging is an intricate process modulated by different molecular and cellular events, such as genome instability, epigenetic and transcriptional changes, molecular damage, cell death and senescence, inflammation, and metabolic dysfunction. Particularly, protein quality control (chaperone systems) tends to be negatively affected by aging, thus leading to cellular senescence in metabolic tissues and, as a consequence, to the increasing dissemination of inflammation throughout the body. The heat shock (HS) response and its associated expression of the 70 kDa family of heat shock proteins (HSP70), which are anti-inflammatory molecular chaperones, are found to be markedly decreased during muscle inactivity and aging, while evidence supports the loss of HSP70 as a key mechanism which may drive muscle atrophy, contractile dysfunction, and reduced regenerative capacity. In addition, abnormal stress response is linked with higher incidence of neurodegenerative diseases as well as low-grade inflammatory diseases that are associated with physical inactivity and obesity. Therefore, strategies to increase or, at least, to maintain the levels of HSP70, and its accompanying HS response to stress, are key to reduce biological cell dysfunctions that occur in aging. In this sense, physical exercise is of note as it is the most powerful inducer of the HS response, comparable only to heat stress and fever-like conditions. On the other hand, the amino acid L-glutamine, whose production within the skeletal muscle and liberation into the blood stream is dependent on muscle activity, is a potentializer of HSP70 expression and HS response, particularly via its entering in hexosamine biosynthetic pathway (HBP). Herein, we discuss the collaborative role of glutamine (and its donors/precursors) and physical exercise (mostly responsible for glutamine release into the circulation) as potential tools to increase HSP70 expression and the HS response in the elderly.

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The Impact of Inflammation on Pancreatic β-Cell Metabolism, Function and Failure in T1DM and T2DM: Commonalities and Differences

Cited by 2 publications

References 154 publications

Hyperoside Supplementation in Preservation Media Surpasses Vitamin C Protection Against Oxidative Stress-Induced Damages in Human Spermatozoa.

Hyperoside Supplementation in Preservation Media Surpasses Vitamin C Protection Against Oxidative Stress-Induced Damages in Human Spermatozoa.

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

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