Age- and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with implications for human type 2 diabetes

Jain, Deepak; Jain, Ruchi; Eberhard, Daniel; Eglinger, Jan; Bugliani, Marco; Piemonti, Lorenzo; Marchetti, Piero; Lammert, Eckhard

doi:10.1093/jmcb/mjs025

Cited by 94 publications

(88 citation statements)

References 62 publications

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“…Our data indicated that impaired Nrf2 activation could potentially be attributed to reduced DJ-1 induced Nrf2 stabilization and increased Nrf2 nuclear export via GSK-3β. Similar findings of reduced DJ-1 expression have been reported in Type-II diabetic mouse models or cell lines [123,124], with a marked correlation between altered lipid metabolism and DJ-1 expression in both rodents and humans [125,126]. In most age-related diabetic pathologies (as well as other Nrf2-related disease pathologies such as cancer), alterations in Nrf2 activation have been strongly linked with Keap1 promoter demethylation [127][128][129][130] as opposed to enhanced DJ-1 methylation [122].…”

Section: Epigenetic Nrf2 Priming Mechanisms In Diabetessupporting

confidence: 86%

Keap1–Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring

Chapple

Puszyk

Mann

2015

Free Radical Biology and Medicine

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Section: Epigenetic Nrf2 Priming Mechanisms In Diabetessupporting

confidence: 86%

Keap1–Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring

Chapple

Puszyk

Mann

2015

Free Radical Biology and Medicine

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“…In fact, some studies have shown that with the ascending of blood glucose, the content of DJ-1 was increased to inhibit the expression of ROS. 27,28 . In addition, the renal protective effects in diabetic rats might be enhanced by the activation of Nrf2.…”

Section: Discussionmentioning

confidence: 99%

The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats

et al. 2015

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Diabetic nephropathy (DN) is one of the most common chronic complications of diabetes, which is associated with an increased oxidative stress induced by hyperglycemia and alterations in DJ-1/NF-E2-related factor-2 (Nrf2) pathway. In the present study, we investigated the role and the proper time nodes of DJ-1/Nrf2 pathway in the pathogenesis of DN. Diabetes mellitus (DM) model of rats was induced by intraperitoneal injection of streptozotocin (STZ) on male Sprague-Dawley (SD) rats. Then, the diabetic rats were divided into 4, 8 and 12 weeks groups. As early at 4 weeks of diabetes, renal histologic evaluation score, cystatin C (Cys C), b2-microglobulin (b2-MG) and malondialdehyde (MDA) levels were increased, and total antioxidative capacity (T-AOC) level was decreased as compared with that in the control group. The protein expressions of DJ-1, NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) were upregulated compared with the control group from 4 weeks and further increased with the progression of DM. The protein expressions of DJ-1, Nrf2 and HO-1 in renal tissues have good line correlations with renal histologic evaluation score, respectively. Taken together, these results suggested that the activation of DJ-1/Nrf2 pathway was involved in the pathogenesis of diabetic nephropathy in rats.ARTICLE HISTORY

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“…Its mutations have been linked to familial forms of Parkinson disease (40,41). Park7 expression is reduced in pancreatic islets of type 2 diabetic patients, where it may be required for mitochondrial function and glucosestimulated insulin secretion (42). Cerebrospinal, but not plasma, Park7 levels have been proposed as a biomarker of Parkinson disease (43,44), whereas 4-hydroxy-2-nonenal-modified Park7 could be a plasma biomarker of late-stage Parkinson (45).…”

Section: Discussionmentioning

confidence: 99%

Altered Plasma Profile of Antioxidant Proteins as an Early Correlate of Pancreatic β Cell Dysfunction

Kuo

Kim-Muller

McGraw

et al. 2016

Journal of Biological Chemistry

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Insulin resistance and ␤ cell dysfunction contribute to the pathogenesis of type 2 diabetes. Unlike insulin resistance, ␤ cell dysfunction remains difficult to predict and monitor, because of the inaccessibility of the endocrine pancreas, the integrated relationship with insulin sensitivity, and the paracrine effects of incretins. The goal of our study was to survey the plasma response to a metabolic challenge in order to identify factors predictive of ␤ cell dysfunction. To this end, we combined (i) the power of unbiased iTRAQ (isobaric tag for relative and absolute quantification) mass spectrometry with (ii) direct sampling of the portal vein following an intravenous glucose/arginine challenge (IVGATT) in (iii) mice with a genetic ␤ cell defect. By so doing, we excluded the effects of peripheral insulin sensitivity as well as those of incretins on ␤ cells, and focused on the first phase of insulin secretion to capture the early pathophysiology of ␤ cell dysfunction. We compared plasma protein profiles with ex vivo islet secretome and transcriptome analyses. We detected changes to 418 plasma proteins in vivo, and detected changes to 262 proteins ex vivo. The impairment of insulin secretion was associated with greater overall changes in the plasma response to IVGATT, possibly reflecting metabolic instability. Reduced levels of proteins regulating redox state and neuronal stress markers, as well as increased levels of coagulation factors, antedated the loss of insulin secretion in diabetic mice. These results suggest that a reduced complement of antioxidants in response to a mixed secretagogue challenge is an early correlate of future ␤ cell failure.The incidence of diabetes has increased considerably (1). Type 2 diabetes is characterized by insulin resistance and impaired ␤ cell function (2). Both abnormalities contribute to the onset and progression of the disease. However, progression from pre-diabetes to diabetes is characterized by a steep decrease of insulin secretory function, whereas insulin resistance remains relatively constant (3, 4). It appears that even modest elevations of plasma glucose levels are toxic to ␤ cells (5). In addition, outcome studies have consistently demonstrated that diabetic patients treated with sulfonylurea-type secretagogues experience faster therapeutic failure rates that require the addition of a second medication, when compared with those treated with insulin sensitizers (6). These facts point to two conclusions: (i) that there is an intrinsic impairment of ␤ cell function in diabetes; and (ii) that promoting insulin secretion does not redress the problem.To develop better therapies and increase the sensitivity of probing ␤ cell function, it would be desirable to have markers predictive of ␤ cell failure. Sensitive tests of insulin secretion are rarely applicable as routine diagnostics, and have limited predictive value of response to treatment. Given the renewed focus on durability as a key criterion to develop more efficacious diabetes treatments (7), it is essential to eva...

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Age- and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with implications for human type 2 diabetes

Cited by 94 publications

References 62 publications

Keap1–Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring

Keap1–Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring

The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats

Altered Plasma Profile of Antioxidant Proteins as an Early Correlate of Pancreatic β Cell Dysfunction

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