Endocrine Abstracts

Background: Inflammatory skin diseases such as psoriasis induce changes in the skin-secretome, which potentially lead to dysfunction of key metabolic tissues and increased risk of psoriasis co-morbidities, such as type 2 diabetes (T2D). However, the proteins and peptides that make up the skin-secretome remain poorly characterised. Proteomic analysis has identified vimentin, parathymosin, prothymosin-alpha, dermcidin, and desmin as potential skin-secretome factors, which may induce metabolic and inflammatory effects in psoriasis (Evans, 2020). This project investigated the impact of these candidate proteins on mouse pancreatic islet and subcutaneous adipose tissue (sAT) function.

Methods: Pancreatic islets were isolated from 8-week-old CD1 male mice. sAT was collected from male 26-week-old C57BL/6 mice fed either standard or 60% high-fat-high-fructose diet (HFHFD). Islets were treated with recombinant proteins at a range of (patho)physiological concentrations, while sAT was treated with a cocktail treatment (vimentin;500 ng/ml, dermcidin;1000 ng/ml, prothymosin-alpha;1000 ng/ml, parathymosin;1000 ng/ml, desmin;500 ng/ml). Pancreatic islet health was determined by glucose-stimulated insulin secretion (GSIS; radioimmunoassay) and cell apoptosis (caspase-glo 3/7 assay). sAT function was determined by qRT-PCR measurements of gene markers of sAT function and inflammation.

Results: Vimentin;500 ng/ml and prothymosin-alpha;1000 ng/ml islet treatments decreased GSIS, whereas parathymosin;1000 ng/ml, dermcidin;1000 ng/ml, and desmin;500 ng/ml increased GSIS, with parathymosin;1000 ng/ml and dermcidin;1000 ng/ml also inducing significantly elevated levels of cytokine-mediated cell apoptosis (P < 0.01). Cocktail treatment of mouse sAT induced a significant increase in expression of IL-1β, IL6, and LCN2 (P < 0.01), along with a significant reduction in the expression of functional markers GLUT4 and PPAR-γ (P < 0.05) both in the standard and 60% HFHFD samples.

Conclusion: Distinct factors present in the skin-secretome could orchestrate the impaired metabolic function observed in psoriasis, possibly through inducing changes in the functional and secretory profile of sAT and islets that could exert systemic effects on key metabolic organs, increasing the risk of T2D.