Mitochondrial dysfunction and pancreatic islet β-cell failure (Review)

Pancreatic β-cells are the only source of insulin in humans. Mitochondria uses pyruvate to produce ATP as an intermediate link between glucose intake and insulin secretion in β-cells, in a process known as glucose-stimulated insulin secretion (GSIS). Previous studies have demonstrated that GSIS is negatively regulated by various factors in the mitochondria, including tRNA(Leu) mutations, high p58 expression, reduced nicotinamide nucleotide transhydrogenase activity, abnormal levels of uncoupling proteins and reduced expression levels of transcription factors A, B1 and B2. Additionally, oxidative stress damages mitochondria and impairs antioxidant defense mechanisms, leading to the increased production of reactive oxygen species, which induces β-cell dysfunction. Inflammation in islets can also damage β-cell physiology. Inflammatory cytokines trigger the release of cytochrome c from the mitochondria via the NF-κB pathway. The present review examined the potential factors underlying mitochondrial dysfunction and their association with islet β-cell failure, which may offer novel insights regarding future strategies for the preservation of mitochondrial function and enhancement of antioxidant activity for individuals with diabetes mellitus.