Effects of dietary glutamine on inflammatory mediator gene expressions in rats with streptozotocin-induced diabetes

Tsai, Pei Hsuan; Yeh, Chui Li; Liu, Jun Jen; Chiu, Wan‐Chun; Yeh, Sung Ling

doi:10.1016/j.nut.2011.06.003

Cited by 19 publications

(14 citation statements)

References 36 publications

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“…Recent reports have described reductions in circulating levels of L-glutamine in diabetes (Etgen & Oldham 2000, Wijekoon et al 2004, Menge et al 2010, Tsai et al 2012. The absence of 2 mM Ala-Gln lowered cellular L-glutamine levels and compromised the GSH concentration in the b-cells as described herein (Table 1).…”

Section: Discussionsupporting

confidence: 55%

“…Furthermore, L-glutamine is a potent modulator of the heat shock protein (HSP) response, possibly through the activation of the glucosamine biosynthetic pathway (HBP) and nutrient sensors such as sirtuin 1 (SIRT1) . Interestingly, in T2DM patients, the concentration of the most abundant amino acid in the body, L-glutamine, may be reduced (approximately 20%), when compared with concentrations in healthy subjects (Menge et al 2010, Tsai et al 2012. In addition, in fatty diabetic animal models, the gluconeogenic amino acids, which include L-glutamine, are progressively reduced in plasma, liver and skeletal muscle (Wijekoon et al 2004).…”

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: 55%

Section: Introductionmentioning

confidence: 99%

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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show abstract

“…Diabetic fed with a common semi purified diet, 3. Identical diet with glutamine 25% of total amino acid nitrogen 8 weeks Significant decrease GPx, SOD, Significant increase TAC, catalase, GRd, GSSG No significant change HDL, TG, LDL, TC, fasting glucose Tsia, Taiwan, 2012 [ 22 ] Rats divided into three groups: 1. Normal control, 2.…”

Section: Resultsmentioning

confidence: 99%

A comprehensive insight into the effect of glutamine supplementation on metabolic variables in diabetes mellitus: a systematic review

et al. 2020

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Diabetes mellitus is one of the most important threats to human health in the twenty-first century. The use of complementary and alternative medicine to prevent, control, and reduce the complications of diabetes mellitus is increasing at present. Glutamine amino acid is known as a functional food. The purpose of this systematic review is to determine the potential role of glutamine supplementation on metabolic variables in diabetes mellitus. For this review, PubMed, SCOPUS, Embase, ProQuest, and Google Scholar databases were searched from inception through April 2020. All clinical trial and animal studies assessing the effects of glutamine on diabetes mellitus were eligible for inclusion. 19 studies of 1482 articles met the inclusion criteria. Of the 19 studies, nine studies reported a significant increase in serum GLP-1 levels. Also, eight studies showed reducing in serum levels of fasting blood sugar, four studies reducing in postprandial blood sugar, and triglyceride after glutamine supplementation. Although glutamine resulted in a significant increase in insulin production in seven studies, the findings on Hb-A1c levels were inconclusive. In addition to, despite of the results was promising for the effects of glutamine on weight changes, oxidative stress, and inflammation, more precise clinical trials are needed to obtain more accurate results. In conclusion, glutamine supplementation could improve glycemic control and levels of incretins (such as GLP-1 and GIP) in diabetes mellitus. However, more studies are needed for future studies.

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“…In the present study, the TNF-α levels in the liver homogenates of the model group were significantly higher compared with the control group (P<0.05); however, the levels in the glutamine treatment group were lower than those in the model group (P<0.05), which was consistent with previous studies. Tsai et al (21) fed diabetic SD rats with 1 kg forage supplemented with 41.7 g glutamine and observed that the mRNA expression of serum inflammatory cytokines, such as TNF-α, interleukin (IL)-6 and transforming growth factor-β, was significantly decreased in the glutamine intervention group compared with the diabetic rats fed a normal diet. Glutamine has also been shown to enhance heat shock protein (HSP) expression in the gut and plasma, as well as to reduce the level of inflammatory cytokines, such as IL-6 and IL-8, thus protecting against inflammatory injury (22).…”

Section: Discussionmentioning

confidence: 99%

Effects of glutamine on oxidative stress and nuclear factor-κB expression in the livers of rats with nonalcoholic fatty liver disease

Lin

Cai

Lin

et al. 2013

Experimental and Therapeutic Medicine

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The aim of this study was to investigate the effects of glutamine on the histomorphology of the liver, oxidative stress and nuclear factor-κB (NF-κB) expression in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD was induced in rats by a high-fat diet, and rats in the treatment group were subjected to oral administration of glutamine (1 g/kg/day). Rats from the treatment, model and normal control groups were assessed after 8 and 12 weeks (n=6 per group at each time-point). The levels of glutathione (GSH), malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in the liver, and the liver histopathology and NF-κB protein 65 (p65) expression in the liver were assessed. Compared with the control group under the same experimental period, the MDA and TNF-α levels in the liver, the hepatic steatosis and the hepatic expression of NF-κB p65 were significantly higher in the model and the treatment groups (P<0.05), while the GSH levels in the liver were significantly lower (P<0.05). These indices improved significantly in the treatment group compared with the model group (P<0.05). In conclusion, glutamine reduces the degree of oxidative stress in the liver, inhibits NF-κB p65 expression and improves hepatic steatosis. Glutamine has a certain protective effect in NAFLD.

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Effects of dietary glutamine on inflammatory mediator gene expressions in rats with streptozotocin-induced diabetes

Cited by 19 publications

References 36 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

A comprehensive insight into the effect of glutamine supplementation on metabolic variables in diabetes mellitus: a systematic review

Effects of glutamine on oxidative stress and nuclear factor-κB expression in the livers of rats with nonalcoholic fatty liver disease

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