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The human batokine ...
The human batokine EPDR1 regulates β-cell metabolism and function
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- Cataldo, Luis Rodrigo (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,University of Copenhagen
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- Gao, Qian (author)
- University of Copenhagen
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- Argemi-Muntadas, Lidia (author)
- University of Copenhagen
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- Hodek, Ondrej (author)
- Sveriges lantbruksuniversitet,Swedish University of Agricultural Sciences, Umeå,Institutionen för skoglig genetik och växtfysiologi,Department of Forest Genetics and Plant Physiology
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- Cowan, Elaine (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Hladkou, Sergey (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Gheibi, Sevda (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Spégel, Peter (author)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Prasad, Rashmi B. (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Eliasson, Lena (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Scheele, Camilla (author)
- University of Copenhagen
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- Fex, Malin (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Mulder, Hindrik (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Moritz, Thomas (author)
- Sveriges lantbruksuniversitet,Swedish University of Agricultural Sciences, Umeå,University of Copenhagen,Institutionen för skoglig genetik och växtfysiologi,Department of Forest Genetics and Plant Physiology
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(creator_code:org_t)
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- Elsevier BV, 2022
- 2022
- English.
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In: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 66
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Abstract
Subject headings
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- Objective: Ependymin-Related Protein 1 (EPDR1) was recently identified as a secreted human batokine regulating mitochondrial respiration linked to thermogenesis in brown fat. Despite that EPDR1 is expressed in human pancreatic β-cells and that glucose-stimulated mitochondrial metabolism is critical for stimulus-secretion coupling in β-cells, the role of EPDR1 in β-cell metabolism and function has not been investigated. Methods: EPDR1 mRNA levels in human pancreatic islets from non-diabetic (ND) and type 2 diabetes (T2D) subjects were assessed. Human islets, EndoC-βH1 and INS1 832/13 cells were transfected with scramble (control) and EPDR1 siRNAs (EPDR1-KD) or treated with human EPDR1 protein, and glucose-stimulated insulin secretion (GSIS) assessed by ELISA. Mitochondrial metabolism was investigated by extracellular flux analyzer, confocal microscopy and mass spectrometry-based metabolomics analysis. Results: EPDR1 mRNA expression was upregulated in human islets from T2D and obese donors and positively correlated to BMI of donors. In T2D donors, EPDR1 mRNA levels negatively correlated with HbA1c and positively correlated with GSIS. EPDR1 silencing in human islets and β-cell lines reduced GSIS whereas treatment with human EPDR1 protein increased GSIS. Epdr1 silencing in INS1 832/13 cells reduced glucose- and pyruvate- but not K+-stimulated insulin secretion. Metabolomics analysis in Epdr1-KD INS1 832/13 cells suggests diversion of glucose-derived pyruvate to lactate production and decreased malate-aspartate shuttle and the tricarboxylic acid (TCA) cycle activity. The glucose-stimulated rise in mitochondrial respiration and ATP/ADP-ratio was impaired in Epdr1-deficient cells. Conclusion: These results suggests that to maintain glucose homeostasis in obese people, upregulation of EPDR1 may improve β-cell function via channelling glycolysis-derived pyruvate to the mitochondrial TCA cycle.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Beta cells
- Insulin secretion
- Lactate
- Mitochondrial metabolism
- TCA cycle
- Type 2 diabetes
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Cataldo, Luis Ro ...
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Gao, Qian
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Argemi-Muntadas, ...
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Hodek, Ondrej
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Cowan, Elaine
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Hladkou, Sergey
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show more...
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Gheibi, Sevda
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Spégel, Peter
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Prasad, Rashmi B ...
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Eliasson, Lena
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Scheele, Camilla
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Fex, Malin
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Mulder, Hindrik
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Moritz, Thomas
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Molecular Metabo ...
- By the university
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Lund University
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Swedish University of Agricultural Sciences