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Mathematical modeling of white adipocyte exocytosis predicts adiponectin secretion and quantifies the rates of vesicle exo- and endocytosis
University of Gothenburg, Sweden.
Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
University of Gothenburg, Sweden.
Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
Vise andre og tillknytning
2017 (engelsk)Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 292, nr 49, s. 20032-20043Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Adiponectin is a hormone secreted from white adipocytes and takes part in the regulation of several metabolic processes. Although the pathophysiological importance of adiponectin has been thoroughly investigated, the mechanisms controlling its release are only partly understood. We have recently shown that adiponectin is secreted via regulated exocytosis of adiponectin-containing vesicles, that adiponectin exocytosis is stimulated by cAMP-dependent mechanisms, and that Ca2+ and ATP augment the cAMP-triggered secretion. However, much remains to be discovered regarding the molecular and cellular regulation of adiponectin release. Here, we have used mathematical modeling to extract detailed information contained within our previously obtained high-resolution patch-clamp time-resolved capacitance recordings to produce the first model of adiponectin exocytosis/secretion that combines all mechanistic knowledge deduced from electrophysiological experimental series. This model demonstrates that our previous understanding of the role of intracellular ATP in the control of adiponectin exocytosis needs to be revised to include an additional ATP-dependent step. Validation of the model by introduction of data of secreted adiponectin yielded a very close resemblance between the simulations and experimental results. Moreover, we could show that Ca2+-dependent adiponectin endocytosis contributes to the measured capacitance signal, and we were able to predict the contribution of endocytosis to the measured exocytotic rate under different experimental conditions. In conclusion, using mathematical modeling of published and newly generated data, we have obtained estimates of adiponectin exo- and endocytosis rates, and we have predicted adiponectin secretion. We believe that our model should have multiple applications in the study of metabolic processes and hormonal control thereof.

sted, utgiver, år, opplag, sider
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC , 2017. Vol. 292, nr 49, s. 20032-20043
Emneord [en]
adipocyte; adipokine; adiponectin; electrophysiology; endocytosis; exocytosis; mathematical modeling
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-143907DOI: 10.1074/jbc.M117.801225ISI: 000417696400009PubMedID: 28972187OAI: oai:DiVA.org:liu-143907DiVA, id: diva2:1170044
Merknad

Funding Agencies|Swedish Diabetes Foundation [DIA2015-062]; Goljes Memory Fund; Swedish Medical Research Council [2010-2656, 2013-7107]; AstraZeneca; European Union [607842]

Tilgjengelig fra: 2018-01-02 Laget: 2018-01-02 Sist oppdatert: 2018-01-02

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