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Minor Role of Mitochondrial Respiration for Fatty-Acid Induced Insulin Secretion
Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal 14558, Germany
Institute for Diabetes and Obesity, Helmholtz Centre Munich, Munich 85764, Germany
* Author to whom correspondence should be addressed.
Received: 15 May 2013; in revised form: 3 September 2013 / Accepted: 10 September 2013 / Published: 16 September 2013
Abstract: An appropriate insulin secretion by pancreatic beta-cells is necessary to maintain glucose homeostasis. A rise in plasma glucose leads to increased metabolism and an elevated cytoplasmic ATP/ADP ratio that finally triggers insulin granule exocytosis. In addition to this triggering pathway, one or more amplifying pathways—activated by amino acids or fatty acid—enhance secretion by promoting insulin granule recruitment to, and priming at, the plasma membrane. The aim of this study was to clarify the impact of the mitochondrial respiratory activity on fatty acid-induced insulin secretion that was assessed by an extracellular flux analyzer. Treatment of isolated mouse islets with glucose (20 mM) increased insulin secretion 18-fold and correlated with ATP-synthesizing respiration. Furthermore, oxygen consumption rate (OCR) significantly increased by 62% in response to glucose, whereas the addition of palmitate resulted only in a minor increase of OCR at both 2.8 mM (11%) and 20 mM glucose (21%). The addition of palmitate showed a pronounced increase of coupling efficiency (CE) at 2.8 mM glucose but no further insulin secretion. However, treatment with palmitate at 20 mM glucose increased insulin secretion about 32-fold accompanied by a small increase in CE. Thus, fatty acid induced respiration has a minor impact on insulin secretion. Our data clearly demonstrate that fatty acids in contrast to glucose play a minor role for respiration-mediated insulin secretion. In the presence of high glucose, fatty acids contribute partially to amplifying pathways of insulin secretion by further increasing mitochondrial activity in the islets of Langerhans.
Keywords: pancreatic islets; insulin secretion; respiratory activity; coupling efficiency
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MDPI and ACS Style
Schulz, N.; Kluth, O.; Jastroch, M.; Schürmann, A. Minor Role of Mitochondrial Respiration for Fatty-Acid Induced Insulin Secretion. Int. J. Mol. Sci. 2013, 14, 18989-18998.
Schulz N, Kluth O, Jastroch M, Schürmann A. Minor Role of Mitochondrial Respiration for Fatty-Acid Induced Insulin Secretion. International Journal of Molecular Sciences. 2013; 14(9):18989-18998.
Schulz, Nadja; Kluth, Oliver; Jastroch, Martin; Schürmann, Annette. 2013. "Minor Role of Mitochondrial Respiration for Fatty-Acid Induced Insulin Secretion." Int. J. Mol. Sci. 14, no. 9: 18989-18998.