Oral supplementations with free and dipeptide forms of l-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins

Cruzat, Vinícius Fernandes; Pantaleão, Lucas Carminatti; Donato, José; Bittencourt, Paulo Ivo Homem de; Tirapegui, Júlio

doi:10.1016/j.jnutbio.2013.11.009

Cited by 68 publications

(89 citation statements)

References 47 publications

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“…Enhanced HUR may promote the stability of numerous target mRNAs, including that encoding SIRT1, via association of HUR with the 3 0 -untranslated region of Sirt1 mRNA, that promotes its stability and thus a rise in Sirt1 expression (Newsholme & de Bittencourt 2014). In turn, SIRT1 enhances the expression of the main heat shock factor, HSF1, and heat shock elements (HSEs) in the nuclei, resulting in expression of HSP70 (Kotas et al 2013, Cruzat et al 2014a, Petry et al 2014, as observed herein (Fig. 5B).…”

Section: Discussionsupporting

confidence: 54%

“…[ [ stress and inflammation (Cruzat et al 2010, 2014a, Krause et al 2011, Petry et al 2014. GSH acts as a scavenger system and has the ability to counteract reactive oxygen species (ROS, e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Both amino acids are also important for the synthesis of the tripeptide L-g-glutamyl-L-cysteinylglycine (GSH, i.e. a major component of the L-glutamine-GSH axis; Cunningham et al 2005, Cruzat et al 2014a, Petry et al 2014. GSH has many protective functions in cellular metabolism, as well as attenuation of oxidative stress and inflammation under catabolic situations (Cruzat & Tirapegui 2009, Cruzat et al 2014b.…”

Section: Introductionmentioning

confidence: 99%

“…Hence, L-glutamine together with L-alanine supplied as the L-alanyl-L-glutamine dipeptide (Ala-Gln) may benefit the antioxidant system, attenuating inflammation, and may modulate the HSP response in catabolic situations (Cruzat et al 2014a,b, Newsholme et al 2014. A metabolic hallmark of diabetes is the aberrant alteration of glucose and lipid concentrations in the blood.…”

Section: Introductionmentioning

confidence: 99%

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Alanyl-glutamine improves pancreatic β-cell function following ex vivo inflammatory challenge

Cruzat¹,

Keane²,

Scheinpflug³

et al. 2014

Journal of Endocrinology

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Obesity-associated diabetes and concomitant inflammation may compromise pancreatic b-cell integrity and function. L-glutamine and L-alanine are potent insulin secretagogues, with antioxidant and cytoprotective properties. Herein, we studied whether the dipeptide L-alanyl-L-glutamine (Ala-Gln) could exert protective effects via sirtuin 1/HUR (SIRT1/HUR) signalling in b-cells, against detrimental responses following ex vivo stimulation with inflammatory mediators derived from macrophages (IMMs). The macrophages were derived from blood obtained from obese subjects. Macrophages were exposed (or not) to lipopolysaccharide (LPS) to generate a pro-inflammatory cytokine cocktail. The cytokine profile was determined following analysis by flow cytometry. Insulin-secreting BRIN-BD11 b-cells were exposed to IMMs and then cultured with or without Ala-Gln for 24 h. Chronic insulin secretion, the L-glutamineglutathione (GSH) axis, and the level of insulin receptor b (IR-b), heat shock protein 70 (HSP70), SIRT1/HUR, CCAAT-enhancer-binding protein homologous protein (CHOP) and cytochrome c oxidase IV (COX IV) were evaluated. Concentrations of cytokines, including interleukin 1b (IL1b), IL6, IL10 and tumour necrosis factor alpha (TNFa) in the IMMs, were higher following exposure to LPS. Subsequently, when b-cells were exposed to IMMs, chronic insulin secretion, and IR-b and COX IV levels were decreased, but these effects were partially or fully attenuated by the addition of Ala-Gln. The glutamine-GSH axis and HSP70 levels, which were compromised by IMMs, were also restored by Ala-Gln, possibly due to protection of SIRT1/HUR levels, and a reduction of CHOP expression. Using an ex vivo inflammatory approach, we have demonstrated Ala-Gln-dependent b-cell protection mediated by coordinated effects on the glutamine-GSH axis, and the HSP pathway, maintenance of mitochondrial metabolism and stimulus-secretion coupling essential for insulin release.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Alanyl-glutamine improves pancreatic β-cell function following ex vivo inflammatory challenge

Cruzat¹,

Keane²,

Scheinpflug³

et al. 2014

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Indeed, glutamine may increase HSP70, BCL2 expression and GSH content, which may reduce TNFa-and IL1b-induced injury and inflammation, an effect partially dependent on nitric oxide (NO) production . Although the mechanism is not completely understood, recent work has demonstrated that other HSPs, such as HSP27 (HSPB1) and HSP90 (HSP90AA1), operate as chaperones promoting protection (Cruzat et al 2013(Cruzat et al , 2014. HSPs provide a protein management system including quality control of damaged proteins, such as those impacted by oxidation and degradation, via the ubiquitin-proteasome system (UPS) (Pratt et al 2010).…”

Section: Nutrient Metabolism and Insulin Action In Target Tissuesmentioning

confidence: 99%

Nutrient regulation of insulin secretion and action

Newsholme

Cruzat

Keane

2014

Journal of Endocrinology

185

128

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Pancreatic b-cell function is of critical importance in the regulation of fuel homoeostasis, and metabolic dysregulation is a hallmark of diabetes mellitus (DM). The b-cell is an intricately designed cell type that couples metabolism of dietary sources of carbohydrates, amino acids and lipids to insulin secretory mechanisms, such that insulin release occurs at appropriate times to ensure efficient nutrient uptake and storage by target tissues. However, chronic exposure to high nutrient concentrations results in altered metabolism that impacts negatively on insulin exocytosis, insulin action and may ultimately lead to development of DM. Reduced action of insulin in target tissues is associated with impairment of insulin signalling and contributes to insulin resistance (IR), a condition often associated with obesity and a major risk factor for DM. The altered metabolism of nutrients by insulin-sensitive target tissues (muscle, adipose tissue and liver) can result in high circulating levels of glucose and various lipids, which further impact on pancreatic b-cell function, IR and progression of the metabolic syndrome. Here, we have considered the role played by the major nutrient groups, carbohydrates, amino acids and lipids, in mediating b-cell insulin secretion, while also exploring the interplay between amino acids and insulin action in muscle. We also focus on the effects of altered lipid metabolism in adipose tissue and liver resulting from activation of inflammatory processes commonly observed in DM pathophysiology. The aim of this review is to describe commonalities and differences in metabolism related to insulin secretion and action, pertinent to the development of DM.

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Unveiling the Neutral Forms of Glutamine

et al. 2019

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Neutral glutamine has been evaporated by laser ablation of its solid sample to seed a rare gas carrier prior to a supersonic expansion and proved by Fourier transform microwave techniques. We report on three distinct neutral conformers that show a singular non‐interacting and flexible amide sidechain in contrast with the other proteinogenic aliphatic amino acids. It could explain the essential biological role of glutamine as a nitrogen source, and its unique ability to form a variety of hydrogen bonds with peptide backbones. Common computational methods fail to predict the delicate balance of intramolecular interactions controlling the geometry of the most stable conformer. The spectroscopic data here reported can be used to benchmark novel computational methods in quantum chemistry.

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Oral supplementations with free and dipeptide forms of l-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins

Cited by 68 publications

References 47 publications

Alanyl-glutamine improves pancreatic β-cell function following ex vivo inflammatory challenge

Alanyl-glutamine improves pancreatic β-cell function following ex vivo inflammatory challenge

Nutrient regulation of insulin secretion and action

Unveiling the Neutral Forms of Glutamine

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