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Sökning: id:"swepub:oai:lup.lub.lu.se:4569dd79-74bc-4dce-8ed1-c5257fc2c8d2" > Enhanced mitochondr...

  • Fex, MalinLund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups (författare)

Enhanced mitochondrial metabolism may account for the adaptation to insulin resistance in islets from C57BL/6J mice fed a high-fat diet.

  • Artikel/kapitelEngelska2007

Förlag, utgivningsår, omfång ...

  • 2006-11-09
  • Springer Science and Business Media LLC,2007
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:4569dd79-74bc-4dce-8ed1-c5257fc2c8d2
  • https://lup.lub.lu.se/record/163326URI
  • https://doi.org/10.1007/s00125-006-0464-4DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

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

Anmärkningar

  • Aim/hypothesis Hyperinsulinaemia maintains euglycaemia in insulin-resistant states. The precise cellular mechanisms by which the beta cells adapt are still unresolved. A peripherally derived cue, such as increased circulating fatty acids, may instruct the beta cell to initiate an adaptive programme to maintain glucose homeostasis. When this fails, type 2 diabetes ensues. Because mitochondria play a key role in beta cell pathophysiology, we tested the hypothesis that mitochondrial metabolism is critical for beta cell adaptation to insulin resistance. Methods C57BL/6J mice were given high-fat (HF) diet for 12 weeks. We then analysed islet hormone secretion, metabolism in vivo and in vitro, and beta cell morphology. Results HF diet resulted in insulin resistance and glucose intolerance but not frank diabetes. Basal insulin secretion was elevated in isolated islets from HF mice with almost no additional response provoked by high glucose. In contrast, a strong secretory response was seen when islets from HF mice were stimulated with fuels that require mitochondrial metabolism, such as glutamate, glutamine, alpha-ketoisocaproic acid and succinate. Moreover, while glucose oxidation was impaired in islets from HF mice, oxidation of glutamine and palmitate was enhanced. Ultrastructural analysis of islets in HF mice revealed an accumulation of lipid droplets in beta cells and a twofold increase in mitochondrial area. Conclusions/interpretation We propose that beta cells exposed to increased lipid flux in insulin resistance respond by increasing mitochondrial volume. This expansion is associated with enhanced mitochondrial metabolism as a means of beta cell compensation. Electronic supplementary material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00125-006-0464-4 and is accessible to authorised users.

Ämnesord och genrebeteckningar

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

  • Dekker Nitert, MarloesLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)medk-mad (författare)
  • Wierup, NilsLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)mphy-nwi (författare)
  • Sundler, FrankLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)mphy-fsu (författare)
  • Ling, CharlotteLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-cl0 (författare)
  • Mulder, HindrikLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)medk-hmu (författare)
  • Celiaki och diabetesForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Diabetologia: Springer Science and Business Media LLC50:1, s. 74-831432-04280012-186X

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