Amino acids and diabetes: implications for endocrine, metabolic and immune function

Newsholme, Philip; Abdulkader, Fernando; Rebelato, Eduardo; Romanatto, Talita; Pinheiro, Carlos; Vitzel, Kaio Fernando; Silva, Erica Portioli; Bazotte, Roberto Barbosa; Procópio, Joaquim; Curi, Rui; Gorjão, Renata; Pithon-Curi, Tânia Cristina

doi:10.2741/3690

Cited by 45 publications

(43 citation statements)

References 234 publications

(251 reference statements)

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“…GSH is a well-known intracellular scavenger of free radicals with detoxification, and it can be biosynthesized in the body from the amino acids L-cysteine, L-glutamic acid, and glycine (Newsholme et al 2011). GSH reduces disulfide bonds formed within cytoplasmic proteins to cysteines by serving as an electron donor.…”

Section: The Role Of Nrf2 In Protecting Against Oxidative Stress-indumentioning

confidence: 99%

The role of Nrf2 in oxidative stress-induced endothelial injuries

Chen¹,

Lu²,

Chen³

et al. 2015

Journal of Endocrinology

335

244

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Endothelial dysfunction is an important risk factor for cardiovascular disease, and it represents the initial step in the pathogenesis of atherosclerosis. Failure to protect against oxidative stress-induced cellular damage accounts for endothelial dysfunction in the majority of pathophysiological conditions. Numerous antioxidant pathways are involved in cellular redox homeostasis, among which the nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is perhaps the most prominent. Nrf2, a transcription factor with a high sensitivity to oxidative stress, binds to AREs in the nucleus and promotes the transcription of a wide variety of antioxidant genes. Nrf2 is located in the cytoskeleton, adjacent to Keap1. Keap1 acts as an adapter for cullin 3/ring-box 1-mediated ubiquitination and degradation of Nrf2, which decreases the activity of Nrf2 under physiological conditions. Oxidative stress causes Nrf2 to dissociate from Keap1 and to subsequently translocate into the nucleus, which results in its binding to ARE and the transcription of downstream target genes. Experimental evidence has established that Nrf2-driven free radical detoxification pathways are important endogenous homeostatic mechanisms that are associated with vasoprotection in the setting of aging, atherosclerosis, hypertension, ischemia, and cardiovascular diseases. The aim of the present review is to briefly summarize the mechanisms that regulate the Nrf2/Keap1-ARE signaling pathway and the latest advances in understanding how Nrf2 protects against oxidative stress-induced endothelial injuries. Further studies regarding the precise mechanisms by which Nrf2-regulated endothelial protection occurs are necessary for determining whether Nrf2 can serve as a therapeutic target in the treatment of cardiovascular diseases.

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Section: The Role Of Nrf2 In Protecting Against Oxidative Stress-indumentioning

confidence: 99%

The role of Nrf2 in oxidative stress-induced endothelial injuries

Chen¹,

Lu²,

Chen³

et al. 2015

Journal of Endocrinology

335

244

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“…Diabetes mellitus can cause skeletal muscle damage and atrophy by the direct effects of high glucose and low insulin [4]. Muscle wasting in diabetes is ultimately the result of damage to the intracellular signaling pathways that are involved in maintaining the balance between synthesis and degradation of protein [5], [6]. Many researches have proved that IGF-1 can inhibit skeletal muscle atrophy by inreasing protein synthesis via activation Akt/mTOR pathways [7]–[9], Besides, IGF-1 can prevent skeletal muscle atrophy by inhibiting protein degradation via the Akt/FoxO pathways [7], [9]–[11].…”

Section: Introductionmentioning

confidence: 99%

Reversal of Muscle Atrophy by Zhimu-Huangbai Herb-Pair via Akt/mTOR/FoxO3 Signal Pathway in Streptozotocin-Induced Diabetic Mice

et al. 2014

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Skeletal muscle atrophy is one of the serious complications of diabetes. Zhimu-Huangbai herb-pair (ZB) is widely used in Chinese traditional medicine formulas for treating Xiaoke (known as diabetes) and its complications. However, the effect of ZB on reversal of muscle atrophy and the underlying mechanisms remain unknown. In this research, we investigated the effect and possible mechanisms of ZB on skeletal muscle atrophy in diabetic mice. Animal model of diabetic muscle atrophy was developed by high fat diet (HFD) feeding plus streptozotocin (STZ) injection. After oral adminstration of ZB for 6 weeks, the effects of ZB on reversal of muscle atrophy and the underlying mechanisms were evaluated by biochemical, histological and western blot methods. The skeletal muscle weight, strength, and cross-sectional area of diabetic mice were significantly increased by ZB treatment. Biochemical results showed that ZB treatment reduced the serum glucose level, and elevated the serum insulin-like growth factor 1 (IGF-1) and insulin levels significantly compared with untreated diabetic group. The western blot results showed that ZB activated the mTOR signal pathway, shown as increased phosphorylations (p-) of Akt, mTOR, Raptor, S6K1 and reduced Foxo3 expression compared with the model group. ZB could reverse muscle atrophy in diabetic mice. This may be through activation of mTOR signaling pathway that promotes protein synthesis, and inactivation foxo3 protein that inhibits protein degradation. These findings suggested that ZB may be considered as a potential candidate drug in treatment of diabetic muscle atrophy.

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“…29,51 Elevated levels of these AA may partly mediate the effect of high protein intake on concentrations of hormones in plasma. 52 Regulation of antioxidative and detoxification reactions NEAA are critical for antioxidative defenses and removal of toxic substances (both xenobiotics and endogenous metabolites) through: (1) synthesis of glutathione from cysteine, glutamate, and glycine; of carnosine from b-alanine and histidine; of creatine from arginine and glycine; and of taurine from cysteine; (2) production of antioxidative enzymes (e.g. glutathione peroxidase, superoxide dismutase, and H 2 O 2 peroxidase); (3) removal of ammonia, oxidants, and xenobiotics; and (4) anti-inflammation and regulation of apoptosis in cells.…”

Section: Regulation Of Endocrine Statusmentioning

confidence: 99%

“…49,52 Specifically, tyrosine is the precursor for synthesis of epinephrine, norepinephrine, dopamine, and thyroid hormones. High concentrations of arginine and glutamine are potent secretagogues for the release of insulin and growth hormone in mammals through NO-and NADHdependent mechanisms, 52 whereas glycine stimulates Figure 3 Proposed mechanisms for arginine to reduce obesity in animals. Arginine activates the cGMP and AMPK signaling pathways, thereby enhancing substrate oxidation in a cell-specific manner and decreasing the accretion of white adipose tissue in the body.…”

Section: Regulation Of Endocrine Statusmentioning

confidence: 99%

Dietary essentiality of “nutritionally non-essential amino acids” for animals and humans

Hou

Yin

2015

Exp Biol Med (Maywood)

242

127

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Based on growth or nitrogen balance, amino acids (AA) had traditionally been classified as nutritionally essential (indispensable) or non-essential (dispensable) for animals and humans. Nutritionally essential AA (EAA) are defined as either those AA whose carbon skeletons cannot be synthesized de novo in animal cells or those that normally are insufficiently synthesized de novo by the animal organism relative to its needs for maintenance, growth, development, and health and which must be provided in the diet to meet requirements. In contrast, nutritionally non-essential AA (NEAA) are those AA which can be synthesized de novo in adequate amounts by the animal organism to meet requirements for maintenance, growth, development, and health and, therefore, need not be provided in the diet. Although EAA and NEAA had been described for over a century, there are no compelling data to substantiate the assumption that NEAA are synthesized sufficiently in animals and humans to meet the needs for maximal growth and optimal health. NEAA play important roles in regulating gene expression, cell signaling pathways, digestion and absorption of dietary nutrients, DNA and protein synthesis, proteolysis, metabolism of glucose and lipids, endocrine status, men and women fertility, acid-base balance, antioxidative responses, detoxification of xenobiotics and endogenous metabolites, neurotransmission, and immunity. Emerging evidence indicates dietary essentiality of ''nutritionally non-essential amino acids'' for animals and humans to achieve their full genetic potential for growth, development, reproduction, lactation, and resistance to metabolic and infectious diseases. This concept represents a new paradigm shift in protein nutrition to guide the feeding of mammals (including livestock), poultry, and fish.

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Amino acids and diabetes: implications for endocrine, metabolic and immune function

Cited by 45 publications

References 234 publications

The role of Nrf2 in oxidative stress-induced endothelial injuries

The role of Nrf2 in oxidative stress-induced endothelial injuries

Reversal of Muscle Atrophy by Zhimu-Huangbai Herb-Pair via Akt/mTOR/FoxO3 Signal Pathway in Streptozotocin-Induced Diabetic Mice

Dietary essentiality of “nutritionally non-essential amino acids” for animals and humans

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