scholarly journals Increased monocyte-derived reactive oxygen species in type 2 diabetes: role of endoplasmic reticulum stress

2017 ◽  
Vol 102 (2) ◽  
pp. 139-153 ◽  
Author(s):  
Robert M. Restaino ◽  
Shekhar H. Deo ◽  
Alan R. Parrish ◽  
Paul J. Fadel ◽  
Jaume Padilla
Keyword(s):  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Role of Perivascular Adipose Tissue on Vascular Reactive Oxygen Species in Type 2 Diabetes: A Give-and-Take Relationship: Figure 1

Diabetes ◽  
2015 ◽  
Vol 64 (6) ◽  
pp. 1904-1906 ◽  
Author(s):  
Jaume Padilla ◽  
Victoria J. Vieira-Potter ◽  
Guanghong Jia ◽  
James R. Sowers
Keyword(s):  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Perivascular Adipose Tissue

Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species

2007 ◽  
Vol 293 (5) ◽  
pp. E1311-E1319 ◽  
Author(s):  
Edward R. Duncan ◽  
Simon J. Walker ◽  
Vivienne A. Ezzat ◽  
Stephen B. Wheatcroft ◽  
Jian-Mei Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Wild Type

Insulin resistance is well established as an independent risk factor for the development of type 2 diabetes and cardiovascular atherosclerosis. Most studies have examined atherogenesis in models of severe insulin resistance or diabetes. However, by the time of diagnosis, individuals with type 2 diabetes already demonstrate a significant atheroma burden. Furthermore, recent studies suggest that, even in adolescence, insulin resistance is a progressive disorder that increases cardiovascular risk. In the present report, we studied early mechanisms of reduction in the bioavailability of the antiatheroscerotic molecule nitric oxide (NO) in very mild insulin resistance. Mice with haploinsufficiency for the insulin receptor (IRKO) are a model of mild insulin resistance with preserved glycemic control. We previously demonstrated that 2-mo-old (Young) IRKO mice have preserved vasorelaxation responses to ACh. This remained the case at 4 mo of age. However, by 6 mo, despite no significant deterioration in glucose homeostasis (Adult), IRKO mice had marked blunting of ACh-mediated vasorelaxation [IRKO maximum contraction response (Emax) 66 ± 5% vs. wild type 87 ± 4%, P < 0.01]. Despite the endothelial dysfunction demonstrated, aortic endothelial nitric oxide synthase (eNOS) mRNA levels were similar in Adult IRKO and wild-type mice, and, interestingly, aortic eNOS protein levels were increased, suggesting a compensatory upregulation in the IRKO. We then examined the potential role of reactive oxygen species in mediating early endothelial dysfunction. The superoxide dismutase mimetic Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) restored ACh relaxation responses in the Adult IRKO (Emax to ACh with MnTMPyP 85 ± 5%). Dihydroethidium fluorescence of aortas and isolated coronary microvascular endothelial cells confirmed a substantial increase in endothelium-derived reactive oxygen species in IRKO mice. These data demonstrate that mild insulin resistance is a potent substrate for accelerated endothelial dysfunction and support a role for endothelial cell superoxide production as a mechanism underlying the early reduction in NO bioavailability.

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