Sökning: onr:"swepub:oai:lup.lub.lu.se:be6c2aba-8b8b-4b50-aad4-a22ea306509b" > Inhibition of the m...
Fältnamn | Indikatorer | Metadata |
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000 | 05059naa a2200457 4500 | |
001 | oai:lup.lub.lu.se:be6c2aba-8b8b-4b50-aad4-a22ea306509b | |
003 | SwePub | |
008 | 160401s2015 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/74254442 URI |
024 | 7 | a https://doi.org/10.1042/BJ201406972 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Stamenkovic, Jelenau Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups4 aut0 (Swepub:lu)med-jsm |
245 | 1 0 | a Inhibition of the malate-aspartate shuttle in mouse pancreatic islets abolishes glucagon secretion without affecting insulin secretion |
264 | 1 | c 2015 |
520 | a Altered secretion of insulin as well as glucagon has been implicated in the pathogenesis of Type 2 diabetes (T2D), but the mechanisms controlling glucagon secretion from alpha-cells largely remain unresolved. Therefore, we studied the regulation of glucagon secretion from alpha TC1-6 (alpha TC1 clone 6) cells and compared it with insulin release from INS-1 832/13 cells. We found that INS-1 832/13 and alpha TC1-6 cells respectively secreted insulin and glucagon concentration-dependently in response to glucose. In contrast, tight coupling of glycolytic and mitochondrial metabolism was observed only in INS-1 832/13 cells. Although glycolytic metabolism was similar in the two cell lines, TCA (tricarboxylic acid) cycle metabolism, respiration and ATP levels were less glucose-responsive in alpha TC1-6 cells. Inhibition of the malate-aspartate shuttle, using phenyl succinate (PhS), abolished glucose-provoked ATP production and hormone secretion from alpha TC1-6 but not INS-1 832/13 cells. Blocking the malate-aspartate shuttle increased levels of glycerol 3-phosphate only in INS-1 832/13 cells. Accordingly, relative expression of constituents in the glycerol phosphate shuttle compared with malate-aspartate shuttle was lower in alpha TC1-6 cells. Our data suggest that the glycerol phosphate shuttle augments the malate-aspartate shuttle in INS-1 832/13 but not alpha TC1-6 cells. These results were confirmed in mouse islets, where PhS abrogated secretion of glucagon but not insulin. Furthermore, expression of the rate-limiting enzyme of the glycerol phosphate shuttle was higher in sorted primary beta-than in alpha-cells. Thus, suppressed glycerol phosphate shuttle activity in the alpha-cell may prevent a high rate of glycolysis and consequently glucagon secretion in response to glucose. Accordingly, pyruvate-and lactate-elicited glucagon secretion remains unaffected since their signalling is independent of mitochondrial shuttles. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng |
653 | a coupling factors | |
653 | a glucose metabolism | |
653 | a mitochondrial transport | |
653 | a islets | |
653 | a insulin | |
653 | a glucagon | |
700 | 1 | a Andersson, Lottau Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups4 aut0 (Swepub:lu)med-laa |
700 | 1 | a Adriaenssens, Alice E.4 aut |
700 | 1 | a Bagge, Annikau Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups4 aut0 (Swepub:lu)med-aib |
700 | 1 | a Sharoyko, Vladimiru Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine4 aut0 (Swepub:lu)med-vrs |
700 | 1 | a Gribble, Fiona4 aut |
700 | 1 | a Reimann, Frank4 aut |
700 | 1 | a Wollheim, Claesu Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Geneva4 aut0 (Swepub:lu)med-cwe |
700 | 1 | a Mulder, Hindriku Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups4 aut0 (Swepub:lu)medk-hmu |
700 | 1 | a Spégel, Peteru Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups4 aut0 (Swepub:lu)tekn-psp |
710 | 2 | a Diabetes - molekylär metabolismb Forskargrupper vid Lunds universitet4 org |
773 | 0 | t Biochemical Journalg 468, s. 49-63q 468<49-63x 0264-6021 |
856 | 4 | u http://dx.doi.org/10.1042/BJ20140697y FULLTEXT |
856 | 4 8 | u https://lup.lub.lu.se/record/7425444 |
856 | 4 8 | u https://doi.org/10.1042/BJ20140697 |
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