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• W2022228039 endingPage "1032" @default.
• W2022228039 startingPage "1019" @default.
• W2022228039 abstract "Pancreatic beta cells are specialised endocrine cells that continuously sense the levels of blood sugar and other fuels and, in response, secrete insulin to maintain normal fuel homeostasis. During postprandial periods an elevated level of plasma glucose rapidly stimulates insulin secretion to decrease hepatic glucose output and promote glucose uptake into other tissues, principally muscle and adipose tissues. Beta cell mitochondria play a key role in this process, not only by providing energy in the form of ATP to support insulin secretion, but also by synthesising metabolites (anaplerosis) that can act, both intra- and extramitochondrially, as factors that couple glucose sensing to insulin granule exocytosis. ATP on its own, and possibly modulated by these coupling factors, triggers closure of the ATP-sensitive potassium channel, resulting in membrane depolarisation that increases intracellular calcium to cause insulin secretion. The metabolic imbalance caused by chronic hyperglycaemia and hyperlipidaemia severely affects mitochondrial metabolism, leading to the development of impaired glucose-induced insulin secretion in type 2 diabetes. It appears that the anaplerotic enzyme pyruvate carboxylase participates directly or indirectly in several metabolic pathways which are important for glucose-induced insulin secretion, including: the pyruvate/malate cycle, the pyruvate/citrate cycle, the pyruvate/isocitrate cycle and glutamate-dehydrogenase-catalysed alpha-ketoglutarate production. These four pathways enable 'shuttling' or 'recycling' of these intermediate(s) into and out of mitochondrion, allowing continuous production of intracellular messenger(s). The purpose of this review is to present an account of recent progress in this area of central importance in the realm of diabetes and obesity research." @default.
• W2022228039 created "2016-06-24" @default.
• W2022228039 creator A5006957202 @default.
• W2022228039 creator A5026986628 @default.
• W2022228039 creator A5037504318 @default.
• W2022228039 creator A5041094606 @default.
• W2022228039 date "2010-03-12" @default.
• W2022228039 modified "2023-10-17" @default.
• W2022228039 title "Regulation of insulin secretion: role of mitochondrial signalling" @default.
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