Decreased Blood Activity of Glucose-6-Phosphate Dehydrogenase Associates with Increased Risk for Diabetes Mellitus

Wan, Gwo-Hwa; Tsai, Shu-Chen; Chiu, Daniel T.

doi:10.1385/endo:19:2:191

Cited by 59 publications

(30 citation statements)

References 18 publications

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“…In the heart, G6PD deficiency may decrease diet-induced oxidative stress and flux through other nonoxidative glucose pathways, thus providing cardioprotection. Our results are consistent with clinical observation that G6PD-deficient people have less cardiovascular disease despite increasing diabetes and kidney dysfunction (12,42,47,58,74,75) and suggest that further clinical investigation into the interaction between G6PD deficiency and obesity is warranted.…”

Section: E966supporting

confidence: 90%

“…Clinical evidence suggests that G6PD deficiency may lead to metabolic dysfunction while decreasing cardiovascular disease (12,19,42,47,58,68,74). Thus, we hypothesized that G6PD deficiency would exacerbate metabolic dysfunction caused by diet-induced obesity (DIO) or high fructose intake while decreasing diet induced cardiac pathology.…”

mentioning

confidence: 99%

“…The risk of developing heart disease is strongly associated with obesity, metabolic dysfunction, and diabetes (17). However, despite its possible cardioprotective role, G6PD deficiency may increase the risk of diabetes (47,58,68,74). Studies in G6PD deficient (G6PDX) mice found that G6PD deficiency may increase ␤-cell apoptosis and result in insulin resistance (79).…”

mentioning

confidence: 99%

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Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets

Hecker

Mapanga

Kimar

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human enzymopathy that affects cellular redox status and may lower flux into nonoxidative pathways of glucose metabolism. Oxidative stress may worsen systemic glucose tolerance and cardiometabolic syndrome. We hypothesized that G6PD deficiency exacerbates diet-induced systemic metabolic dysfunction by increasing oxidative stress but in myocardium prevents diet-induced oxidative stress and pathology. WT and G6PD-deficient (G6PDX) mice received a standard high-starch diet, a high-fat/high-sucrose diet to induce obesity (DIO), or a high-fructose diet. After 31 wk, DIO increased adipose and body mass compared with the high-starch diet but to a greater extent in G6PDX than WT mice (24 and 20% lower, respectively). Serum free fatty acids were increased by 77% and triglycerides by 90% in G6PDX mice, but not in WT mice, by DIO and high-fructose intake. G6PD deficiency did not affect glucose tolerance or the increased insulin levels seen in WT mice. There was no diet-induced hypertension or cardiac dysfunction in either mouse strain. However, G6PD deficiency increased aconitase activity by 42% and blunted markers of nonoxidative glucose pathway activation in myocardium, including the hexosamine biosynthetic pathway activation and advanced glycation end product formation. These results reveal a complex interplay between diet-induced metabolic effects and G6PD deficiency, where G6PD deficiency decreases weight gain and hyperinsulinemia with DIO, but elevates serum free fatty acids, without affecting glucose tolerance. On the other hand, it modestly suppressed indexes of glucose flux into nonoxidative pathways in myocardium, suggesting potential protective effects.

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Section: E966supporting

confidence: 90%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets

Hecker

Mapanga

Kimar

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…Clinically, G6PD deficiency, affecting over 200 million individuals worldwide, can cause neonatal jaundice, drug-or infection-induced haemolytic crisis, favism and, less commonly, non-spherocytic haemolytic anaemia (Beutler, 1991;Luzzatto & Battistuzzi, 1985). Moreover, it is associated with poor prognosis in patients with nasopharyngeal carcinoma (Cheng et al, 2001) and with increased risk for diabetes mellitus (Wan et al, 2002). Given its important physiological role in nucleated cells, G6PD deficiency may cause more health problems than previously thought.…”

Section: Introductionmentioning

confidence: 99%

Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection

Cheng

Weng

et al. 2008

Journal of General Virology

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Variations in the cellular microenvironment affect the host's susceptibility to pathogens. Using glucose-6-phosphate dehydrogenase (G6PD)-deficient fibroblasts as a model, this study demonstrated that the cellular redox status affects infectivity as well as the outcome of enterovirus 71 (EV71) infection. Compared with their normal counterparts, G6PD-deficient cells supported EV71 replication more efficiently and showed greater cytopathic effect and loss of viability. Mechanistically, viral infection led to increased oxidative stress, as indicated by increased dichlorofluorescein fluorescence and a diminished ratio of glutathione (GSH) to its disulfide form (GSSG), with the effect being greater in G6PD-deficient cells. Exogenous expression of active G6PD in the deficient cells, which increased the intracellular GSH : GSSG ratio, suppressed the generation of viral progeny. Consistent with this, treatment with N-acetylcysteine offered resistance to EV71 propagation and a cytoprotective effect on the infected cells. These findings support the notion that G6PD status, and thus redox balance, is an important determinant of enteroviral infection.

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“…[10][11][12] In its reduced form glutathione (GSH), a small tripeptide, is the main non-enzymatic antioxidant in the RBC and readily undergoes oxidation to the dimer (GSSG) to protect such important cellular components as proteins from oxidant insults (figure 1). [13][14][15] Under normal conditions, cells are capable of regenerating GSH at the expense of the reducing factor nicotinamide adenine dinucleotide phosphate (NADPH). Though other cells have several methods to produce NADPH, RBCs rely solely on the enzyme glucose-6-phosphate dehydrogenase (G6PD) for regeneration of NADPH, thereby rendering G6PD activity important to the antioxidant status of the RBC.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of cell aging and ATP release from erythrocytes and its implications in type 2 diabetes

Subasinghe¹,

Spence²

2008

Analytica Chimica Acta

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Glucose-6-phosphate dehydrogenase (G6PD) is a determinant in the antioxidant status of the red blood cell (RBC) and is also used as an indicator of cell age. However, it is unknown if the relationship between antioxidant status, cell age, and RBC-derived adenosine triphosphate (ATP) occurs immediately or over a period of time. Therefore, the development of a simultaneous determination of G6PD activity (via the determination of nicotinamide adenine dinucleotide phosphate (NADPH)) in RBCs and the determination of deformation-induced RBC-derived ATP is described. The NADPH and ATP were determined while undergoing a chemically-induced aging process via inhibition of G6PD with dehydroepiandroesterone (DHEA). Upon incubation with DHEA for 30 minutes, NADPH levels measured in a flow stream decreased to 7.96 ± 1.10 μM from an original value of 13.20 ± 1.80 μM in a 0.02% solution of RBCs. In order to demonstrate a direct relationship between G6PD activity and deformation-induced ATP release from RBCs, a simultaneous microflow determination of G6PD activity and ATP release was performed. Upon inhibition with DHEA, NADPH levels decreased to 8.62 ± 0.29 μM from its original value of 12.73 ± 0.50 μM while ATP release decreased from 0.21 ± 0.07 μM to 0.06 ± 0.02 μM. These values were validated by an examination of NADPH levels in, and ATP release from, RBC fractions containing younger and older cells (separated by cell density centrifugation). This determination provides evidence that antioxidant status in the RBC and its ability to release ATP, a known stimulus of nitric oxide production, are closely related.

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Decreased Blood Activity of Glucose-6-Phosphate Dehydrogenase Associates with Increased Risk for Diabetes Mellitus

Cited by 59 publications

References 18 publications

Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets

Effects of glucose-6-phosphate dehydrogenase deficiency on the metabolic and cardiac responses to obesogenic or high-fructose diets

Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection

Simultaneous determination of cell aging and ATP release from erythrocytes and its implications in type 2 diabetes

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