Glycine Increases Insulin Sensitivity and Glutathione Biosynthesis and Protects against Oxidative Stress in a Model of Sucrose‐Induced Insulin Resistance

Abstract

Oxidative stress and redox status play a central role in the link between insulin resistance (IR) and lipotoxicity in metabolic syndrome. This mechanistic link may involve alterations in the glutathione redox state. We examined the effect of glycine supplementation to diet on glutathione biosynthesis, oxidative stress, IR, and insulin cell signaling in liver from sucrose-fed (SF) rats characterized by IR and oxidative stress. Our hypothesis is that the correction of glutathione levels by glycine treatment leads to reduced oxidative stress, a mechanism associated with improved insulin signaling and IR. Glycine treatment decreases the levels of oxidative stress markers in liver from SF rats and increases the concentrations of glutathione (GSH) and γ-glutamylcysteine and the amount of γ-glutamylcysteine synthetase (γ-GCS), a key enzyme of GSH biosynthesis in liver from SF rats. In liver from SF rats, glycine also decreases the insulin-induced phosphorylation of insulin receptor substrate-1 (ISR-1) in serine residue and increases the phosphorylation of insulin receptor β-subunit (IR-β) in tyrosine residue. Thus, supplementing diets with glycine to correct GSH deficiency and to reduce oxidative stress provides significant metabolic benefits to SF rats by improving insulin sensitivity.

Glycine increases glyoxalase‐1 function by promoting nuclear factor erythroid 2‐related factor 2 translocation into the nucleus of kidney cells of streptozotocin‐induced diabetic rats

“…In the present study, glycine treatment significantly enhanced the nuclear translocation of Nrf2, and increased the mRNA expression of Nrf2‐targeted genes, such as Glo1, CAT, SOD2, HO‐1, NQO1 and GPx‐1, suggesting that the Nrf2 pathway was activated. The activities of SOD and CAT were also increased after glycine treatment, which is consistent with previous studies, but the mechanism remains unclear. One speculation is that glycine increases the level of GSH, which has been reported to increase SOD activity by abolishing reactive oxygen species‐induced inactivation.…”

“…It was suggested that glycine is rate‐limiting for GSH synthesis. Under diabetes or metabolic syndrome, the level of GSH is reduced, but this reduction can be reversed by glycine treatment. Our previous study showed that the levels of glycine in both serum and kidneys were decreased in diabetic rats, but were restored after oral glycine treatment.…”

“…GSH is crucial for the detoxifying process catalyzed by Glo1, and depletion of GSH can suppress the function of Glo1 and induce significant MG accumulation. In individuals with either diabetes or metabolic syndrome, the levels of glycine and GSH are reduced as compared with healthy individuals, but this reduction can be reversed after oral glycine treatment. We have previously reported that oral supplement of glycine can inhibit the AGE/RAGE signaling pathway and the subsequent oxidative stress in the kidneys of diabetic rats, but whether this beneficial effect is associated with the upregulation of Glo1 still remains unknown.…”

Short-Term Exposure to High Sucrose Levels near Weaning Has a Similar Long-Lasting Effect on Hypertension as a Long-Term Exposure in Rats

“…The importance of regulating factors of eNOS expression, such as elevated levels of circulating insulin and insulin resistance (HOMA-IR index) is possibly different in both conditions, since insulin levels and HOMA-IR were increased in LTS rats but not in STS rats. Decreased insulin sensitivity and insulin resistance had already been reported in the MS rats that received the same treatment as our LTS group by using the euglycemic clamp technique [ 54 ]. The severity of the alterations in insulin sensitivity in LTS might trigger compensatory mechanisms that are not initiated in a less severe alteration such as STS.…”

Amino acids and the regulation of oxidative stress and immune function in dairy cattle

“…Glycine has also been observed to help ameliorate metabolic syndrome in obesity and diabetes, with growing evidence that Gly supplementation may have therapeutic benefits through improving insulin sensitivity, enhancing antioxidant capacity, and reducing pro-inflammatory cytokines (reviewed previously by Wang et al, 2013 ). For example, when sucrose feeding was used to induce insulin resistance, rats supplemented with Gly had improved insulin sensitivity and increased hepatic concentrations of GSH, Cys, and γ-glutamylcysteine, which could help reduce oxidative stress ( El-Hafidi et al, 2018 ).…”