Basic science: Beta cells, islets and complications

Introduction: Inflammation has been linked to hemichannel-mediated release of adenosine triphosphate (ATP) and downstream fibrosis in various tissue type-specific complications diabetes. In the current study we examined how inflammatory cytokines alter markers renal tubular injury ahead evaluating efficacy connexin-43 (Cx43) hemichannel blocker Tonabersat negating these effects. Methods: Human Kidney (HK-2) proximal tubule epithelial cells were cultured low (5mM) or high (25mM) glucose ± interleukin (IL)-1β (10ng) tumour necrosis factor alpha (TNFα; 10ng) for 48 hours. Immunoblotting determined expression key proteins, whilst carboxyfluorescein (200µM) dye uptake activity treated +/- (10µM). Results: Under conditions, IL-1β TNFα significantly increased 161±16%, (P<0.05, n=5) an effect which was negated when co-incubated with (123±8.5%, n=5). Moreover, stimulation protein IL-6 (206±42%, P<0.05, extracellular matrix fibronectin (365±81%, n=4), collagen-I (516±36%, n=4) collagen-IV (830±217%, P<0.01, as compared control. The augmented at (491±164%, n=5), (455±112%, n=6), (725±85%, colIagen-IV (868±77%, P<0.001, n=6). Conclusion: We demonstrate that IL1β increase profibrotic proteins HK-2 cells. Paralleled by a Tonabersat-sensitive Cx43 activity, believe blocking hemichannels therapeutic potential protects against changes associated diabetic kidney.