Glutamine is a powerful effector of heat shock protein expression in <i>Drosophila</i> Kc cells

Sanders, Marilyn M.; Kon, Christine

doi:10.1002/jcp.1041460123

Cited by 48 publications

(54 citation statements)

References 60 publications

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“…Plasma glucose concentrations were measured by the glucose oxidase method (Glucose Analyzer II; Beckman Instruments, Fullerton, CA). Concentrations of individual plasma amino acids were measured by high-performance liquid chromatography (HPLC) as described (27,28). Plasma FFA concentrations were assayed with a microfluorimetric method (Wako Chemical, Richmond, VA).…”

Section: C] and [mentioning

confidence: 99%

Mechanism of Amino Acid-Induced Skeletal Muscle Insulin Resistance in Humans

et al. 2002

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Plasma concentrations of amino acids are frequently elevated in insulin-resistant states, and a proteinenriched diet can impair glucose metabolism. This study examined effects of short-term plasma amino acid (AA) elevation on whole-body glucose disposal and cellular insulin action in skeletal muscle. Seven healthy men were studied for 5.5 h during euglycemic (5.5 mmol/l), hyperinsulinemic (430 pmol/l), fasting glucagon (65 ng/ l), and growth hormone (0.4 g/l) somatostatin clamp tests in the presence of low (ϳ1.6 mmol/l) and increased (ϳ4.6 mmol/l) plasma AA concentrations. Glucose turnover was measured with D-[6,6-2 H 2 ]glucose. Intramuscular concentrations of glycogen and glucose-6-phosphate (G6P) were monitored using 13 C and 31 P nuclear magnetic resonance spectroscopy, respectively. A ϳ2.1-fold elevation of plasma AAs reduced whole-body glucose disposal by 25% (P < 0.01). Rates of muscle glycogen synthesis decreased by 64% (180 -315 min, 24 ؎ 3; control, 67 ؎ 10 mol ⅐ l ؊1 ⅐ min ؊1 ; P < 0.01), which was accompanied by a reduction in G6P starting at 130 min (⌬G6P 260 -300 min , 18 ؎ 19; control, 103 ؎ 33 mol/l; P < 0.05). In conclusion, plasma amino acid elevation induces skeletal muscle insulin resistance in humans by inhibition of glucose transport/phosphorylation, resulting in marked reduction of glycogen synthesis. Diabetes 51:599 -605, 2002 P lasma concentrations of alanine and particularly branched-chain amino acids (AAs) are elevated in insulin-resistant states such as obesity (1,2), and high dietary protein intake impairs glucose metabolism mainly by changing the utilization of gluconeogenic precursors (3-6).The mechanisms by which AAs could reduce skeletal muscle glucose uptake are as yet unclear. At the cellular level, availability of substrates for energy production, such as AAs and free fatty acids (FFAs), may play an important role in modulating the response to insulin (7). In vitro studies demonstrated that AAs may inhibit glucose utilization in skeletal muscle at various levels. AAs could decrease glucose oxidation by substrate competition with glucose (8,9) and/or reduce glucose uptake (10) by interaction with early steps of insulin signaling (11). Studies in humans, however, revealed controversial results. Infusion of AAs decreased forearm and whole-body glucose disposal in some (12-15), but not all (16,17), studies. Moreover, endogenous release of insulin (18) and glucagon (19) induced by plasma AA elevation might have obscured possible direct effects of AAs in those studies. Taking together all these factors, it is uncertain whether AAs directly induce skeletal muscle insulin resistance in vivo and if so, which mechanism (glucose uptake versus substrate competition) is responsible for such an effect.This study was therefore designed to examine effects of plasma AA elevation on skeletal muscle glucose metabolism by combining isotope dilution technique with in vivo nuclear magnetic resonance (NMR) spectroscopy of gastrocnemius muscle from healthy young humans. In vivo [ 13 C]NMR spectroscop...

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Section: C] and [mentioning

confidence: 99%

Mechanism of Amino Acid-Induced Skeletal Muscle Insulin Resistance in Humans

et al. 2002

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“…Consequently, glutamine depletion does impair cellular stress response in human leucocytes [254]. In fact, it has long been recognized that the HS response of eukaryotic cells depends on glutamine and/or some glutamine metabolite [255]. Now, it is clear that, besides its classic metabolic roles, glutamine is key for survival and cytoprotection via HBP.…”

Section: Glutamine Depletion States Impair the Heat Shock Responsementioning

confidence: 99%

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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“…As HSPs são consideradas essenciais no processo de recuperação celular. Evidências experimentais indicam que o aumento da disponibilidade de glutamina às células pode aumentar a expressão das HSPs, o que mantém a capacidade da célula em resistir a lesões (31) .…”

Section: Aspectos Moleculares De Ação Da Glutaminaunclassified

Glutamina: aspectos bioquímicos, metabólicos, moleculares e suplementação

Cruzat

Petry

Tirapegui

2009

Rev Bras Med Esporte

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A glutamina é o aminoácido livre mais abundante no plasma e no tecido muscular. Nutricionalmente é classificada como um aminoácido não essencial, uma vez que pode ser sintetizada pelo organismo a partir de outros aminoácidos. A glutamina está envolvida em diferentes funções, tais como a proliferação e desenvolvimento de células, o balanço acidobásico, o transporte da amônia entre os tecidos, a doação de esqueletos de carbono para a gliconeogênese, a participação no sistema antioxidante e outras. Por meio de técnicas de biologia molecular, estudos demonstram que a glutamina pode também influenciar diversas vias de sinalização celular, em especial a expressão de proteínas de choque térmico (HSPs). As HSPs contribuem para a manutenção da homeostasia da célula na presença de agentes estressores, tais como as espécies reativas de oxigênio (ERO). Em situações de elevado catabolismo muscular, como após exercícios físicos intensos e prolongados, a concentração de glutamina pode tornar-se reduzida. A menor disponibilidade desse aminoácido pode diminuir a resistência da célula a lesões, levando a processos de apoptose celular. Por essas razões, a suplementação com L-glutamina, tanto na forma livre, quanto como dipeptídeo, tem sido investigada. Alguns aspectos bioquímicos, metabólicos e mecanismos moleculares da glutamina, bem como os efeitos de sua suplementação, são abordados no presente trabalho.Palavras-chave: glutamina, exercício, HSP, suplementação, dipeptídeo. aBStRaCtGlutamine is the most frequent free amino acid in the serum and muscular tissue. Nutritionally, it is classified as a non-essential amino acid, once it can be synthesized by the body from other amino acids. Glutamine is involved in different functions, such as cell proliferation and development, basic acid balance, ammonia transportation between tissues, carbon skeleton donation to the gluconeogenesis, participation in the antioxidant system, among others. Molecular biology techniques show that it may also influence several cell signaling ways, especially the expression of heat shock proteins (HSP). The HSPs contribute to the maintenance of the cellular homeostasis in the presence of stress agents such as oxygen reactive species (ORE). In situations of high cellular catabolism, as after intense and prolonged physical exercises, the glutamine concentration may become reduced. Lower availability of this amino acid may decrease the cell resistance to injuries, leading to cellular apoptosis processes. Therefore, L-glutamine supplementation either in free form or as dipeptide has been investigated. Some biochemical and metabolic aspects, molecular mechanism of glutamine, as well as the effects of its supplementation are approached in the present article.Keywords: glutamine, exercise, HSP, supplementation, dipeptide. intRodUÇÃoEm 1873, Hlasiwetz e Habermann foram os primeiros a considerar a glutamina como sendo uma molécula com propriedades biologicamente importantes. Posteriormente, novas observações levaram os pesquisadores a pensar que a amônia encontrada...

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Glutamine is a powerful effector of heat shock protein expression in Drosophila Kc cells

Cited by 48 publications

References 60 publications

Mechanism of Amino Acid-Induced Skeletal Muscle Insulin Resistance in Humans

Mechanism of Amino Acid-Induced Skeletal Muscle Insulin Resistance in Humans

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

Glutamina: aspectos bioquímicos, metabólicos, moleculares e suplementação

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