Oxidative Stress in Type 1 Diabetes

Haskins, Kathryn; Bradley, Brenda J.; Powers, Katherine; Fadok, Valerie A.; Flores, Sonia C.; Ling, Xiaofeng; Pugazhenthi, Subbiah; Reusch, Jane E.B.; Kench, Jennifer

doi:10.1196/annals.1288.006

Cited by 166 publications

(120 citation statements)

References 64 publications

(63 reference statements)

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…Moreover, the suppression of oxidative stress has been shown to reduce the abnormally high levels of proinflammatory cytokines in diabetic macrophages. 19 14S,21R-diHDHA was found to decrease ROS generation ( Figure 6), providing another possible means by which 14S,21R-diHDHA treatment mediates recovery of macrophage prohealing functions in diabetes.…”

Section: Discussionmentioning

confidence: 89%

“…Compared with normal macrophages, diabetic macrophages display detrimental pathophysiological responses, such as expressing low levels of angiogenic cytokines, 4,[17][18][19] including reduced expression of VEGF and PDGF-BB (Figure 3). Moreover, the association of decreased formation of 14S,21R-diHDHA with impaired prohealing functions of db/db macrophages indicates that impaired functions of diabetic macrophages also includes impaired formation of this autacoid.…”

Section: Discussionmentioning

confidence: 99%

“…18,19 We therefore investigated whether 14S,21R-diHDHA treatment reduces ROS generation. A high concentration of glucose (25 mmol/L) induced ROS generation in db/ϩ macrophages.…”

Section: S21r-dihdha Reduces Generation Of Ros and Increases Il-10mentioning

confidence: 99%

“…8,16 Diabetes and the accompanying hyperglycemia and oxidative stress damage DNA, proteins, and lipids in various tissues. These conditions cause cellular and enzymatic dysfunction during the formation of cytokines and eicosanoids associated with cell growth, angiogenesis, and/or inflammation, 4,7,[17][18][19] all of which are at least in part responsible for impairment of macrophage functions in diabetes. 18,19 We have observed that 14S,21R-diHDHA formation was significantly halted in diabetic wounds, compared with nondiabetic wounds in mice, which suggests that diabetic complications dysregulate the generation of DHA-derived lipid mediators.…”

mentioning

confidence: 99%

“…These conditions cause cellular and enzymatic dysfunction during the formation of cytokines and eicosanoids associated with cell growth, angiogenesis, and/or inflammation, 4,7,[17][18][19] all of which are at least in part responsible for impairment of macrophage functions in diabetes. 18,19 We have observed that 14S,21R-diHDHA formation was significantly halted in diabetic wounds, compared with nondiabetic wounds in mice, which suggests that diabetic complications dysregulate the generation of DHA-derived lipid mediators. 16 In addition, supplementation of 14S,21R-diHDHA into diabetic wounds counteracts diabetes-associated impairment of wound healing, 16 indicating that 14S,21R-diHDHA is an important prohealing lipid mediator.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

Tian

Lü

Shah

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Impaired macrophage functions imposed by diabetic complications and the suppressed formation of 14S, 2 1 R -d i h y d r o x y d o c o s a -4 Z , 7Z , 1 0 Z , 1 2 E , 1 6 Z , 19Z-hexaenoic acid (14S,21R-diHDHA) in wounds contribute significantly to deficient wound healing in diabetics, but how are macrophage functions and 14S,21R-diHDHA formation associated? We studied 14S,21R-diHDHA generation from macrophages using liquid chromatography/mass spectrometry. The role in macrophage-mediated wound healing functions was determined using a murine splinted excisional wound healing model and in vitro assays. 14S,21R-diHDHA acts as a macrophage-generated autacoid, and its attenuated formation in macrophages of diabetic db/db mice was accompanied by impairment of macrophage prohealing functions. 14S,21R-diHDHA restored db/db macrophage-impaired prohealing functions by promoting wound re-epithelialization, formulation of granulation tissue, and vascularization. Additionally, 12/15-lipoxygenase-deficient macrophages, which are unable to produce 14S,21R-diHDHA, exhibited impaired prohealing functions, which also were restored by 14S,21R-diHDHA treatment. The molecular mechanism for 14S,21R-diHDHA-induced recovery of impaired prohealing functions of db/db macrophages involves enhancing their secretion of vascular endothelial growth factor and platelet-derived growth factor BB, decreasing hyperglycemia-induced generation of reactive oxygen species, and increasing IL-10 expression under inflammatory stimulation. Taken together, these results indicate that deficiency of 14S,21R-diHDHA formation by diabetic macrophages contributes to their impaired prohealing functions. Our findings provide mechanistic insights into wound healing in diabetics and suggest the possibility of using autologous macrophages/monocytes, treated with 14S,21R-diHDHA, or related compounds, to promote diabetes-impaired wound healing. (Am J Pathol

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

“…18,19 We therefore investigated whether 14S,21R-diHDHA treatment reduces ROS generation. A high concentration of glucose (25 mmol/L) induced ROS generation in db/ϩ macrophages.…”

Section: S21r-dihdha Reduces Generation Of Ros and Increases Il-10mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

Tian

Lü

Shah

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

Oral gavage delivery of Cornus officinalis extract delays type 1 diabetes onset and hyperglycemia in non‐obese diabetic (NOD) mice

Fletcher,

Olsson,

Zhang

et al. 2024

FEBS Open Bio

View full text Add to dashboard Cite

Type 1 Diabetes (T1D) is an autoimmune disease initiated by genetic predisposition and environmental influences, which result in the specific destruction of insulin‐producing pancreatic β‐cells. Currently, there are over 1.6 million cases of T1D in the United States with a worldwide incidence rate that has been increasing since 1990. Here, we examined the effect of Cornus officinalis (CO), a well‐known ethnopharmacological agent, on a T1D model of the non‐obese diabetic (NOD) mouse. A measured dose of CO extract was delivered into 10 wk. old NOD mice by oral gavage for 15 weeks. T1D incidence and hyperglycemia were significantly lower in the CO‐treated group as compared to the water gavage (WT) and a no handling or treatment control group (NHT) following treatment. T1D onset per group was 30%, 60% and 86% for the CO, WT and NHT groups, respectively. Circulating C‐peptide was higher, and pancreatic insulitis was decreased in non‐T1D CO treated mice. Our findings suggest that CO may have therapeutic potential as both a safe and effective interventional agent to slow early stage T1D progression.

show abstract

Hydrogen‐Bonded Multilayers of Tannic Acid as Mediators of T‐Cell Immunity

Kozlovskaya

Xue

Lei

et al. 2014

Adv Healthcare Materials

100

View full text Add to dashboard Cite

Type 1 diabetes is an autoimmune-mediated disease resulting in the destruction of insulin-secreting pancreatic β-cells. Transplantation of insulin-producing islets is a viable treatment to restore euglycemia in Type 1 diabetics, however, the clinical application remains limited due to the use of toxic immunosuppressive therapies to prevent immune-mediated rejection. We present a nanothin polymer material with dual antioxidant and immunosuppressive properties capable of modulating both innate and adaptive immune responses crucial for transplantation outcome. Through the use of hollow microparticles (capsules) comprising of hydrogen-bonded multilayers of natural polyphenol (tannic acid) with poly(N-vinylpyrrolidone) (TA/PVPON) and with poly(N-vinylcaprolactam) (TA/PVCL), pro-inflammatory reactive oxygen and nitrogen species are efficiently dissipated and the production of IFN-γ and TNF-α pro-inflammatory cytokines are attenuated by cognate antigen-stimulated autoreactive CD4+ T cells. Our results provide evidence that TA-containing capsules are efficacious in immunomodulation and may provide physical transplant protection and prevent diabetogenic autoreactive T cell responses. Future studies will determine if xeno- and allotransplantation with (TA/PVPON)- or (TA/PVCL)-coated pancreatic islets will decrease the risk of graft rejection due to attenuation of oxidative stress and IFN-γ, and restore euglycemia in Type 1 diabetics.

show abstract

Oxidative Stress in Type 1 Diabetes

Cited by 166 publications

References 64 publications

Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

Oral gavage delivery of Cornus officinalis extract delays type 1 diabetes onset and hyperglycemia in non‐obese diabetic (NOD) mice

Hydrogen‐Bonded Multilayers of Tannic Acid as Mediators of T‐Cell Immunity

Contact Info

Product

Resources

About