Lymphatic system changes in diabetes mellitus: role of insulin and hyperglycemia

Moriguchi, P; Sannomiya, Paulina; Lara, Pedro Fernandes; Oliveira‐Filho, Ricardo Martins; Greco, Karin Vicente; Sudo-Hayashi, Lia Siguemi

doi:10.1002/dmrr.500

Cited by 55 publications

(48 citation statements)

References 46 publications

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“…Suppression of VEGFR-3 reduced lymphangiogenesis at islets and draining LNs; consequently, inflammation decreased, while islets were preserved (80). Moreover, functional alteration of the lymphatic system was also observed in a diabetic rat model (81). In patients with type 2 diabetes, the dermal lymphatic system showed increased lymphatic vessel density and proliferation.…”

Section: Diabetesmentioning

confidence: 92%

Inflammation-associated lymphangiogenesis: a double-edged sword?

Kim¹,

Kataru²,

Koh³

2014

J. Clin. Invest.

195

146

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Lymphangiogenesis and lymphatic vessel remodeling are complex biological processes frequently observed during inflammation. Accumulating evidence indicates that inflammation-associated lymphangiogenesis (IAL) is not merely an endpoint event, but actually a phenomenon actively involved in the pathophysiology of various inflammatory disorders. The VEGF-C/VEGFR-3 and VEGF-A/VEGF-R2 signaling pathways are two of the best-studied pathways in IAL. Methods targeting these molecules, such as prolymphangiogenic or antilymphatic treatments, were found to be beneficial in various preclinical and/or clinical studies. This Review focuses on the most recent achievements in the fields of lymphatic biology relevant to inflammatory conditions. Additionally, preclinical and clinical therapies that modulate IAL are summarized.

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Section: Diabetesmentioning

confidence: 92%

Inflammation-associated lymphangiogenesis: a double-edged sword?

Kim¹,

Kataru²,

Koh³

2014

J. Clin. Invest.

195

146

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“…These include a reduced number of leukocytes in inflammatory lesions (18Y21), reduced mast cell degranulation (22,23), reduced superoxide generation and tumor necrosis factor (TNF) ! release (24), and reduction in lymph node retention capacity (25). These abnormalities might contribute to the increased susceptibility and severity of infections in the diabetic host.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Lipopolysaccharide-Induced Acute Lung Inflammation

Martins¹,

Meyer-Pflug²,

Alba-Loureiro³

et al. 2006

Shock

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The present study was undertaken to investigate the influence of insulin on lipopolysaccharide (LPS)-induced acute lung injury. Diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 30 days) and controls were instilled with saline containing LPS (750 microg/0.4 mL) or saline alone. The following analyses were performed 6 h there after: (a) total and differential cell counts in bronchoalveolar lavage (BAL) fluid, (b) quantification of tumor necrosis factor alpha, interleukin (IL) 1beta, IL-10, and cytokine-induced neutrophil chemoattractant 1 in the BAL (enzyme-linked immunosorbent assay), (c)immunohistochemistry for intercellular adhesion molecule 1 and E-selectin on lung vessels, and (d) quantification of metalloproteinases (MMP) 2 and 9 in the BAL (zymography). Relative to controls, diabetic rats exhibited a reduction in the number of neutrophils (80%) and reduced concentrations of tumor necrosis factor alpha (56%), IL-1beta (66%), and IL-10 (35%) after LPS instillation. Cytokine-induced neutrophil chemoattractant 1 levels did not differ between groups. Increased levels of MMP-2 (90%) and MMP-9 (500%) were observed in diabetic rats compared with controls. Treatment of diabetic rats with neutral protamine Hagedorn insulin (4 IU, s.c.), 2 h before LPS instillation, completely restored the number of neutrophils and concentrations of cytokines in the BAL fluid. Despite no significant differences between diabetic and control groups, there was a remarkable increase in intercellular adhesion molecule 1 and E-selectin expression on lung vessels after insulin treatment. Levels of MMP-2 and MMP-9 did not change after treatment with insulin. Levels of corticosterone were equivalent among groups. Data presented suggest that insulin modulates the production/release of cytokines and the expression of adhesion molecules controlling, therefore, neutrophil migration during the course of LPS-induced acute lung inflammation.

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“…These include decreased microvascular responses to inflammatory mediators such as histamine and bradykinin (3,4), decreased protein leakage and edema formation (5-7), reduced mast cell degranulation (8), decreased leukocyte-endothelial cell interactions and reduced number of leukocytes in inflammatory lesions (9)(10)(11)(12)(13)(14)(15), lowered airway inflammatory response to antigen challenge (16,17), low superoxide generation, and reduced release of tumor necrosis factor-α (TNF-α), interleukin-1ß and prostaglandin E 2 by leukocytes upon exposure to lipopolysaccharide (LPS) (18)(19)(20); low content of arachidonic acid in neutrophils (20), and a reduction in lymph node retention capacity (21). These abnormalities might contribute to the increased susceptibility and severity of infections in diabetic patients.…”

Section: Diabetes Mellitus and Inflammationmentioning

confidence: 99%

Neutrophil function and metabolism in individuals with diabetes mellitus

Alba-Loureiro

Munhoz

Martins

et al. 2007

Braz J Med Biol Res

Self Cite

307

214

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Neutrophils act as first-line-of-defense cells and the reduction of their functional activity contributes to the high susceptibility to and severity of infections in diabetes mellitus. Clinical investigations in diabetic patients and experimental studies in diabetic rats and mice clearly demonstrated consistent defects of neutrophil chemotactic, phagocytic and microbicidal activities. Other alterations that have been reported to occur during inflammation in diabetes mellitus include: decreased microvascular responses to inflammatory mediators such as histamine and bradykinin, reduced protein leakage and edema formation, reduced mast cell degranulation, impairment of neutrophil adhesion to the endothelium and migration to the site of inflammation, production of reactive oxygen species and reduced release of cytokines and prostaglandin by neutrophils, increased leukocyte apoptosis, and reduction in lymph node retention capacity. Since neutrophil function requires energy, metabolic changes (i.e

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Lymphatic system changes in diabetes mellitus: role of insulin and hyperglycemia

Cited by 55 publications

References 46 publications

Inflammation-associated lymphangiogenesis: a double-edged sword?

Inflammation-associated lymphangiogenesis: a double-edged sword?

Modulation of Lipopolysaccharide-Induced Acute Lung Inflammation

Neutrophil function and metabolism in individuals with diabetes mellitus

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