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Mathematical modeli...
Mathematical modeling of white adipocyte exocytosis predicts adiponectin secretion and quantifies the rates of vesicle exo- and endocytosis
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- Brännmark, Cecilia (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,University of Gothenburg, Sweden
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- Lövfors, William (author)
- Linköpings universitet,Avdelningen för medicinsk teknik,Tekniska fakulteten
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- Komai, Ali, 1987 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,University of Gothenburg, Sweden
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- Axelsson, Tom (author)
- Linköpings universitet,Institutionen för medicinsk teknik,Tekniska fakulteten
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- El Hachmane, Michael (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,University of Gothenburg, Sweden
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- Saliha, Musovic, 1990 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,University of Gothenburg, Sweden
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- Paul, Alexandra, 1988 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Chalmers University of Technology, Sweden
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- Nyman, Elin (author)
- Linköpings universitet,Avdelningen för medicinsk teknik,Tekniska fakulteten,AstraZeneca RandD, Sweden
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- Olofsson, Charlotta S, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,University of Gothenburg,University of Gothenburg, Sweden
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(creator_code:org_t)
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017
- 2017
- English.
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In: Journal of Biological Chemistry. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 0021-9258 .- 1083-351X. ; 292:49, s. 20032-20043
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Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- NATURVETENSKAP -- Data- och informationsvetenskap -- Systemvetenskap, informationssystem och informatik (hsv//swe)
- NATURAL SCIENCES -- Computer and Information Sciences -- Information Systems (hsv//eng)
- NATURVETENSKAP -- Matematik -- Matematisk analys (hsv//swe)
- NATURAL SCIENCES -- Mathematics -- Mathematical Analysis (hsv//eng)
- TEKNIK OCH TEKNOLOGIER -- Elektroteknik och elektronik -- Reglerteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Electrical Engineering, Electronic Engineering, Information Engineering -- Control Engineering (hsv//eng)
Keyword
- adipocyte
- adipokine
- adiponectin
- electrophysiology
- endocytosis
- exocytosis
- mathematical
- adrenal chromaffin cells
- pancreatic beta-cells
- 3t3-l1 adipocytes
- insulin-resistance
- camp concentrations
- glucose-transport
- systems-biology
- ca2
- atp
- calcium
- electrophysiology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Brännmark, Cecil ...
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Lövfors, William
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Komai, Ali, 1987
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Axelsson, Tom
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El Hachmane, Mic ...
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Saliha, Musovic, ...
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Paul, Alexandra, ...
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Nyman, Elin
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Olofsson, Charlo ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Computer and Inf ...
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and Information Syst ...
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NATURAL SCIENCES
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and Mathematics
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University of Gothenburg
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Chalmers University of Technology
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Linköping University