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Inhibition of the m...
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Stamenkovic, JelenaLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
(författare)
Inhibition of the malate-aspartate shuttle in mouse pancreatic islets abolishes glucagon secretion without affecting insulin secretion
- Artikel/kapitelEngelska2015
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LIBRIS-ID:oai:lup.lub.lu.se:be6c2aba-8b8b-4b50-aad4-a22ea306509b
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https://lup.lub.lu.se/record/7425444URI
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https://doi.org/10.1042/BJ20140697DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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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.
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Andersson, LottaLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)med-laa
(författare)
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Adriaenssens, Alice E.
(författare)
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Bagge, AnnikaLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)med-aib
(författare)
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Sharoyko, VladimirLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)med-vrs
(författare)
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Gribble, Fiona
(författare)
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Reimann, Frank
(författare)
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Wollheim, ClaesLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University of Geneva(Swepub:lu)med-cwe
(författare)
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Mulder, HindrikLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)medk-hmu
(författare)
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Spégel, PeterLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)tekn-psp
(författare)
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Diabetes - molekylär metabolismForskargrupper vid Lunds universitet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Biochemical Journal468, s. 49-630264-6021
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Stamenkovic, Jel ...
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Andersson, Lotta
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Adriaenssens, Al ...
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Bagge, Annika
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Sharoyko, Vladim ...
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Gribble, Fiona
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Reimann, Frank
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Wollheim, Claes
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Mulder, Hindrik
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Spégel, Peter
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- MEDICIN OCH HÄLSOVETENSKAP
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och Klinisk medicin
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