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

Abstract

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. Contents

Rice Husk Silica Liquid Protects Pancreatic β Cells from Streptozotocin-Induced Oxidative Damage

“…Under the stimulation of oxidative stress, the mitochondrial membrane potential (ΔΨm) will be changed, which is characterized by the disordered membrane potential leads to the opening of mitochondrial pores, thus releases cytochrome C into the cytoplasm, which in turn triggers the downstream apoptotic cascade [22,23]. AI-Nahdi et al RIN-m5F cells are a widely used insulin-secreting cell line, mainly containing insulin and a small amount of glucagon and somatostatin [17].…”

Cytochrome c Oxidase Activity as a Metabolic Regulator in Pancreatic Beta-Cells

“…T2D is preceded by years of prediabetes, during which the elevation of blood glucose exerts deleterious effects on β-cell mitochondria and impairs insulin secretion [2,4,5,8,11,12,[25][26][27]. On the other hand, disrupting the mitochondrial oxidative metabolism blocks GSIS [1][2][3].…”

“…An abnormal mitochondrial morphology and reduced GSIS have been found in β cells from postmortem T2D patients [8][9][10]. Impairments in OxPhos [16,28,29] and diminished mitochondrial activity have been demonstrated in diabetes patients [2,4,11,12,27,[30][31][32][33][34][35], while mutations in the mitochondrial genome such as the mtDNA 3243 mutation were shown to be associated with diabetes [36][37][38][39][40]. More specifically, OxPhos genes were differentially expressed, and DNA methylation was found in these genes in islets from patients with T2D compared with nondiabetic donors [13,14].…”

Effect of Aspirin on Mitochondrial Dysfunction and Stress in the Pancreas and Heart of Goto-Kakizaki Diabetic Rats

“…Oxidative stress plays a key role in the pathophysiology of insulin resistance and diabetes, via various molecular mechanisms, including beta cell dysfunction, inflammatory responses and mitochondrial dysfunction [54,55]. Researchers have also shown that oxidative stress is involved in the pathophysiology of diabetic cardiomyopathy and heart failure [7].…”