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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

Förlag, utgivningsår, omfång ...

  • 2015

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:be6c2aba-8b8b-4b50-aad4-a22ea306509b
  • https://lup.lub.lu.se/record/7425444URI
  • https://doi.org/10.1042/BJ20140697DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Andersson, LottaLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)med-laa (författare)
  • Adriaenssens, Alice E. (författare)
  • Bagge, AnnikaLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)med-aib (författare)
  • 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)
  • Gribble, Fiona (författare)
  • Reimann, Frank (författare)
  • 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)
  • Mulder, HindrikLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)medk-hmu (författare)
  • Spégel, PeterLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups(Swepub:lu)tekn-psp (författare)
  • Diabetes - molekylär metabolismForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Biochemical Journal468, s. 49-630264-6021

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