These findings unravel a more complex picture of the mechanistic effects of cilengitide on endothelial cells and, more generally, highlight the role of integrins and integrin-induced signaling events in the regulation of endothelial cell functions (See Figure 9 for a working model).
Genes showing demethylation were involved in key cell functions (see Supplementary Table S1 for a complete list) that included adhesion and invasion (e.g., cadherins, laminins, keratins), migration (e.g., SLIT family), apoptosis (e.g., Elmo3), and cell trafficking (e.g., CXCL chemokines).
However, this could lead to improved understanding of the complex relationships between regulation of signalling pathways and T-cell function (see Fig. 2).
BRIN-BD11 β-cells represent a useful model for such studies, since they are stable in culture and have well-characterized metabolic, signalling, insulin secretory and cell viability responses to glucose, amino acids and numerous other modulators of β-cell function (see [ 20, 21] for details).
What could account for some of the differences in β-cell function seen in studies with early aggressive insulin therapy?
Given the progressive decline in β-cell function seen in type 2 diabetes, a treatment option that has the potential to preserve β-cell function is optimal.
Bafilomycin from Streptomyces-infected vegetables has been shown to specifically decrease beta-cell function, seen as reduction of islet size and beta-cell mass after injection in mice [ 116, 179].
Taken together, these data from the OGTT, IVGTT and clamp studies, suggests that a number of variables, such as prevailing levels of IGF-I (and indeed the entire GH-IGF-IGFBP axis [ 32]), norepinephrine and triglycerides, and possibly concepts such as glucose toxicity and lipotoxicity, might interact, influence and perhaps explain the perturbed β-cell function seen in this and other studies.
GSOA prioritized gene sets that are clearly related to p53 and cell-cycle function (see Table 2, Additional file 2).
However, the disintegration of the unique islet structure followed by culture and cell sorting involves many treatments that affect cell viability and function (see above), which will reduce the functional integrity of the surface proteome.
