Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip

Diabetes mellitus (DM) is a complex disease with high prevalence of comorbidity and mortality. DM is predicted to reach more than 700 million people by 2045. In recent years, several advanced in vitro models and analytical tools were developed to investigate the pancreatic tissue response to pathological situations and identify therapeutic solutions. Of all the in vitro promising models, cell culture in microfluidic biochip allows the reproduction of in-vivo-like micro-environments. Here, we cultured rat islets of Langerhans using dynamic cultures in microfluidic biochips. The dynamic cultures were compared to static islets cultures in Petri. The islets' exometabolomic signatures, with and without GLP1 and isradipine treatments, were characterized by GC-MS. Compared to Petri, biochip culture contributes to maintaining high secretions of insulin, C-peptide and glucagon. The exometabolomic profiling revealed 22 and 18 metabolites differentially expressed between Petri and biochip on Day 3 and 5. These metabolites illustrated the increase in lipid metabolism, the perturbation of the pentose phosphate pathway and the TCA cycle in biochip. After drug stimulations, the exometabolome of biochip culture appeared more perturbed than the Petri exometabolome. The GLP1 contributed to the increase in the levels of glycolysis, pentose phosphate and glutathione pathways intermediates, whereas isradipine led to reduced levels of lipids and carbohydrates.

Automated summary

Diabetes mellitus is a complex disease with a high prevalence and mortality rate. Advanced in vitro models and analytical tools, such as microfluidic biochips, have been developed to investigate the pancreatic tissue response and identify therapeutic solutions. In this study, rat islets of Langerhans were cultured in microfluidic biochips and compared to static cultures in Petri dishes. The results showed that the biochip culture maintained high secretions of insulin, C-peptide, and glucagon compared to the Petri dish culture. Exometabolomic profiling revealed differential expression of metabolites between the two culture methods, indicating changes in lipid metabolism, the pentose phosphate pathway, and the TCA cycle in the biochip culture. Drug stimulation further perturbed the exometabolome of the biochip culture, with GLP1 leading to an increase in glycolysis and pentose phosphate pathway intermediates, and isradipine causing reduced levels of lipids and carbohydrates.