Abstract
Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane. Gated by cellular stress and injury, they open under pathophysiological conditions and in doing so release ‘danger signals’ including adenosine triphosphate into the extracellular environment. Linked to sterile inflammation via activation of the nod-like receptor protein 3 inflammasome, targeting aberrant hemichannel activity and the release of these danger signals has met with favourable outcomes in multiple models of disease, including secondary complications of diabetes. In this review, we provide a comprehensive update on those studies which document a role for aberrant connexin hemichannel activity in the pathogenesis of both diabetic eye and kidney disease, ahead of evaluating the efficacy of blocking connexin-43 specific hemichannels in these target tissues on tissue health and function.
Highlights
Impacting almost 10% of adults, diabetes is a global healthcare concern that affects an estimated 463 million people worldwide
Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye
The role of hyperglycaemia in regulating connexin expression [43,44], gap junction communication [45] and hemichannel activity [46,47,48] is well documented [49], and of the 21 isoforms known to be expressed within the human body, connexin 43 (Cx43) has been strongly linked to the pathogenesis of multiple secondary complications of diabetes [43,50,51,52]
Summary
Impacting almost 10% of adults, diabetes is a global healthcare concern that affects an estimated 463 million people worldwide. Individuals exhibiting diabetic retinopathy appear more susceptible to the onset of kidney problems [23] These findings suggest a ‘common pathway’ representative of systemic microvascular damage and chronic inflammation that, secondary to diabetes, leads to a progressive loss of tissue function. The role of hyperglycaemia in regulating connexin expression [43,44], gap junction communication [45] and hemichannel activity [46,47,48] is well documented [49], and of the 21 isoforms known to be expressed within the human body, Cx43 has been strongly linked to the pathogenesis of multiple secondary complications of diabetes [43,50,51,52]. Known to underpin disease progression across multiple age associated conditions e.g., diabetes [55], obesity [25] and age-related macular degeneration [57], recent attention has focussed on the design of pharmacological compounds that block key inflammatory candidates, such as the nod-like receptor protein 3 (NLRP3) inflammasome (e.g., MCC950) [58], changes in cell phenotype (e.g., senolytics)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
