Insulin Signaling in Human Adipocytes a Systems Biology Approach

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MARC

Brännmark, Cecilia,1983-Linköpings universitet,Cellbiologi,Hälsouniversitetet (author)

Insulin Signaling in Human Adipocytes a Systems Biology Approach

BookEnglish2012

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Linköping :Linköping University Electronic Press,2012
82 s.
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:liu-85001
ISBN:9789175197890
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-85001URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:vet swepub-contenttype
Subject category:dok swepub-publicationtype

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Linköping University Medical Dissertations,0345-0082 ;1331

Notes

Obesity and a sedentary life style are associated with type 2 diabetes, a disease starting with insulin resistance in the adipose tissue, which spreads to the whole body. Despite large research efforts to understand the insulin signaling system, there is little knowledge of the mechanisms behind insulin resistance and type 2 diabetes developments. We have herein focused on the insulin signaling in adipocytes, elucidating mechanisms for early signaling. We have also modeled isolated adipocytes and data from the in vivo, whole bodysituation, concurrently. We also mapped and quantitatively described differences in the insulin signaling of adipocytes from type 2 diabetics and non-diabetics.In paper I we show that neither insulin degradation, receptor internalization, nor feedback signals can as separate explanations cause the overshoot in tyrosine phosphorylation of IRS1, while an endocytosis-dependent feedback mechanism explains all available data.In paper II we show that it is not possible to scale up the experimentally determined glucose uptake by isolated human adipocytes to match the glucose uptake profile of the whole adipose tissue in vivo. Other insulin effects need to be accounted for.In paper III we show that attenuation of the positive feedback to serine 307 phosphorylation of IRS1 can explain the insulin resistance in the insulin signaling in adipocytes seen in type 2 diabetes. However, to fully explain both the signaling and the glucose uptake, a reduction in the amount of Glut4 is also needed.

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Strålfors, Peter,ProfessorLinköpings universitet,Cellbiologi,Hälsouniversitetet(Swepub:liu)petst48 (thesis advisor)
Cedersund, Gunnar,Dr.Linköpings universitet,Cellbiologi,Hälsouniversitetet(Swepub:liu)gunce57 (thesis advisor)
Arner, Peter,ProfessorInstitutionen för medicin, Karolinska Institutet, Stockholm (opponent)
Linköpings universitetCellbiologi (creator_code:org_t)

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