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- Title
The Insulin Sensitizer Rosiglitazone Decreases Inflammatory Pattern and Improves Vascular Neuroprotection in Insulin-Resistant Type 2 Diabetic Subjects with Alzheimer's Disease.
- Authors
Solerte, Sebastiano B.; Micale, Giuliana; Cantoni, Francesca; Schifino, Nicola; Basso, Cristina; Gazzaruso, Carmine; Locatelli, Eleonora; Fioravanti, Marisa
- Abstract
Insulin resistance could be involved in brain inflammation and metabolic/vascular disorders in diabetes and Alzheimer's disease (AD). In particular, reduced glucose utilization within brain could induce neurodegeneration and dementia of AD and vascular types. In the present study, we measure the secretions of inflammatory cytokines (i.e. TNF-α, IL-6 and IL-8) and of vascular endothelial growth factor (VEGF) secreted by circulating peripheral blood mononuclear cells (PBMC) of elderly Type 2 diabetic subjects with AD (T2AD) diagnosed according to DSM IV-R and NINCDS-ADRDA criteria. Cytokines and VEGF were determined after exposure with glucose (1, 5, 10, 20 mM/ml/10[sup 7] PBMC/cells) and with glucose co-incubated with rosiglitazone (RSG: 00.1, 00.5, 0.1 mg/ml/10[sup 7] PBMC/cells; 57 subjects with T2AD (aged 68-89 yr.) and 55 healthy elderly subjects (HES: aged 71-87 yr.) were recruited for the study. PBMC were separated by Ficoll-Hypaque and gradient centrifugation and were incubated for 20h at 37°C with 5% CO². TNF-α, IL-6, IL-8 and VEGF were measured by highly sensitive ELISA (R&D Systems, USA). HOMA-IR was higher in T2AD than in healthy subjects (2.96±0.4 vs 1.61±0.3, p<0.0001). The spontaneous and glucose-modulated secretions of TNF-α, IL-6, IL-8 were significantly increased (p<0.001) in T2AD compared to HES; whereas VEGF (spontaneous and after TGF-b1 and LPS incubation) was significantly lower (p<0.001) in T2AD than in HES. The co-incubation of PBMC with RSG+glucose significantly suppresses, in a dose dependent manner, TNF-α, IL-6, IL-8 secretions from 60% to 85% by comparison to basal values (p<0.001) in T2AD. On the contrary, RSG significantly increase VEGF production in T2AD. Our data preliminary suggest that RSG normalise or antagonise the glucose-modulated pro-inflammatory activity of PBMC also increasing VEGF-dependent neuroprotection in T2AD. Insulin resistance could be potentially associated with a common pathogenetic mechanism leadind to Type 2 Diabetes and Alzheimer's Disease. (this work was supported by an official grant of the University of Pavia; FAR 2006)
- Subjects
INSULIN resistance; DIABETES complications; ALZHEIMER'S disease; DEMENTIA; CYTOKINES; VASCULAR endothelial growth factors; TUMOR necrosis factors
- Publication
Diabetes, 2007, Vol 56, pA165
- ISSN
0012-1797
- Publication type
Article