Evaluating the modulation of the intracellular production of H2S in the functionality and metabolic activity of primary cultures of pancreatic islets

Abstract

Diabetes Mellitus is a metabolic disease characterized by hyperglycaemia that currently affects one in ten people worldwide. Uncontrolled Diabetes is associated with long-term damage and dysfunction and failure of different organs. Although there are therapies for the treatment of diabetes, they are not strongly effective. In order to develop an appropriate therapy for diabetes, we are studying the modulation of the intracellular production of the gasotransmitter hydrogen sulfide (H2S) in pancreatic islets using a H2S donor (compound α). Mice treated with two doses (5 and 10 μM) of compound α showed increased metabolic activity and oxygen consumption rate in islets exposed to high concentrations of glucose (22 mM) when compared with the untreated control, suggesting that mitochondria are one of the main targets of H2S effects. Importantly, compound α showed increased insulin secretion under high glucose (22 mM) conditions. Lentiviral-mediated overexpression of Cystathionine-beta-synthase and Cystathionine-gamma-lyase, main enzymes that synthesise endogenous H2S, in primary pancreatic islets also showed increased metabolic activity. Taken together, these data indicate that compound α, a H2S generator, increases metabolic activity and produces greater insulin secretion in murine primary pancreatic islets.