5-Hexadecanoyloxyoctadecanoic Acid (5-PAHSA) as a Potential Therapeutic Agent in Diabetes? Preliminary Studies Using the Newly Developed, Fully Functional Islet-on-a-Chip Model  ^†

Abstract

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from a defect in the production or function of insulin, secreted by β cells of the pancreatic islets. Pancreatic islets are spherical cell aggregates (100–200 μm) which consist of several cell types. What is most important for improving research in the field of diabetes is the development of a model that reflects in vivo conditions. Here, we present a study based on the Islet-on-a-chip system, which was designed to create fully functional pseudo-islets (three-dimensional aggregates of α and β cells). This PDMS/PDMS Islet-on-a-chip system consists of two elliptical cell-culture chambers. In each of the chambers, there are 15 round microtraps (280 μm × 280 μm), each of them composed of seven circular micropillars, which force cell aggregation by limiting the growth surface. We designed this device to facilitate the screening of potential therapeutic agents, so here, we examined the effect of the newly discovered compound named 5-PAHSA on the developed model. Due to the appropriate design of the microfluidic system, it was possible to simultaneously culture, observe, and analyze the cell proliferation, viability, and hormone expression after incubation using selected concentrations of 5-PAHSA. It was noticed that after incubation with 5-PAHSA, the degree of proliferation increased in relation to both the control and the previous day of incubation. After analysis of the fluorescence intensity levels, the highest expression of insulin was observed after 48h of incubation with 100 μm of 5-PAHSA. These observations were confirmed by analyzing the amounts of secreted insulin under low (LG, 2.5 mM) and high (HG, 16.5 mM) glucose conditions using the ELISA test. Based on these results, it can be concluded that 5-PAHSA has potential properties for use as a therapeutic agent in diabetes, and the developed microsystem can be used for rapid drug screening.