Drp1 guarding of the mitochondrial network is important for glucose-stimulated insulin secretion in pancreatic beta cells

作者：Reinhardt Florian; Schultz Julia; Waterstradt Rica; Baltrusch Simone^*

来源：Biochemical and Biophysical Research Communications, 2016, 474(4): 646-651.

DOI：10.1016/j.bbrc.2016.04.142

• Pancreatic beta cells
• Dynamin-related protein 1 (Drp1)
• Mitochondrial fission
• Mitochondrial dynamics
• Glucose-stimulated insulin secretion

Mitochondria form a tubular network in mammalian cells, and the mitochondrial life cycle is determined by fission, fusion and autophagy. Dynamin-related protein 1 (Drp1) has a pivotal role in these processes because it alone is able to constrict mitochondria. However, the regulation and function of Drp1 have been shown to vary between cell types. Mitochondrial morphology affects mitochondrial metabolism and function. In pancreatic beta cells mitochondrial metabolism is a key component of the glucose induced cascade of insulin secretion. The goal of the present study was to investigate the action of Drp1 in pancreatic beta cells. For this purpose Drpl was down-regulated by means of shDrp1 in insulin secreting INS1 cells and mouse pancreatic islets. In INS1 cells reduced Drpl expression resulted in diminished expression of proteins regulating mitochondrial fusion, namely mitofusin 1 and 2, and optic atrophy protein 1. Diminished mitochondrial dynamics can therefore be assumed. After down-regulation of Drp1 in INS1 cells and spread mouse islets the initially homogenous mitochondrial network characterised by a moderate level of interconnections shifted towards high heterogeneity with elongated, clustered and looped mitochondria. These morphological changes were found to correlate directly with functional alterations. Mitochondrial membrane potential and ATP generation were significantly reduced in INS1 cells after Drpl down-regulation. Finally, a significant loss of glucose-stimulated insulin secretion was demonstrated in INS1 cells and mouse pancreatic islets. In conclusion, Drpl expression is important in pancreatic beta cells to maintain the regulation of insulin secretion.

• 出版日期2016-6-10
• 单位河北医科大学