@article{cataldo_human_2022,
	title = {The human batokine {EPDR1} regulates β-cell metabolism and function},
	volume = {66},
	issn = {2212-8778},
	url = {https://www.sciencedirect.com/science/article/pii/S2212877822001983},
	doi = {10.1016/j.molmet.2022.101629},
	abstract = {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.},
	language = {en},
	urldate = {2022-12-22},
	journal = {Molecular Metabolism},
	author = {Cataldo, Luis Rodrigo and Gao, Qian and Argemi-Muntadas, Lidia and Hodek, Ondrej and Cowan, Elaine and Hladkou, Sergey and Gheibi, Sevda and Spégel, Peter and Prasad, Rashmi B. and Eliasson, Lena and Scheele, Camilla and Fex, Malin and Mulder, Hindrik and Moritz, Thomas},
	month = dec,
	year = {2022},
	keywords = {Beta cells, Insulin secretion, Lactate, Mitochondrial metabolism, TCA cycle, Type 2 diabetes},
	pages = {101629},
}

{"_id":"yzMEmo5reQ3iZSxHu","bibbaseid":"cataldo-gao-argemimuntadas-hodek-cowan-hladkou-gheibi-spgel-etal-thehumanbatokineepdr1regulatescellmetabolismandfunction-2022","author_short":["Cataldo, L. R.","Gao, Q.","Argemi-Muntadas, L.","Hodek, O.","Cowan, E.","Hladkou, S.","Gheibi, S.","Spégel, P.","Prasad, R. B.","Eliasson, L.","Scheele, C.","Fex, M.","Mulder, H.","Moritz, T."],"bibdata":{"bibtype":"article","type":"article","title":"The human batokine EPDR1 regulates β-cell metabolism and function","volume":"66","issn":"2212-8778","url":"https://www.sciencedirect.com/science/article/pii/S2212877822001983","doi":"10.1016/j.molmet.2022.101629","abstract":"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.","language":"en","urldate":"2022-12-22","journal":"Molecular Metabolism","author":[{"propositions":[],"lastnames":["Cataldo"],"firstnames":["Luis","Rodrigo"],"suffixes":[]},{"propositions":[],"lastnames":["Gao"],"firstnames":["Qian"],"suffixes":[]},{"propositions":[],"lastnames":["Argemi-Muntadas"],"firstnames":["Lidia"],"suffixes":[]},{"propositions":[],"lastnames":["Hodek"],"firstnames":["Ondrej"],"suffixes":[]},{"propositions":[],"lastnames":["Cowan"],"firstnames":["Elaine"],"suffixes":[]},{"propositions":[],"lastnames":["Hladkou"],"firstnames":["Sergey"],"suffixes":[]},{"propositions":[],"lastnames":["Gheibi"],"firstnames":["Sevda"],"suffixes":[]},{"propositions":[],"lastnames":["Spégel"],"firstnames":["Peter"],"suffixes":[]},{"propositions":[],"lastnames":["Prasad"],"firstnames":["Rashmi","B."],"suffixes":[]},{"propositions":[],"lastnames":["Eliasson"],"firstnames":["Lena"],"suffixes":[]},{"propositions":[],"lastnames":["Scheele"],"firstnames":["Camilla"],"suffixes":[]},{"propositions":[],"lastnames":["Fex"],"firstnames":["Malin"],"suffixes":[]},{"propositions":[],"lastnames":["Mulder"],"firstnames":["Hindrik"],"suffixes":[]},{"propositions":[],"lastnames":["Moritz"],"firstnames":["Thomas"],"suffixes":[]}],"month":"December","year":"2022","keywords":"Beta cells, Insulin secretion, Lactate, Mitochondrial metabolism, TCA cycle, Type 2 diabetes","pages":"101629","bibtex":"@article{cataldo_human_2022,\n\ttitle = {The human batokine {EPDR1} regulates β-cell metabolism and function},\n\tvolume = {66},\n\tissn = {2212-8778},\n\turl = {https://www.sciencedirect.com/science/article/pii/S2212877822001983},\n\tdoi = {10.1016/j.molmet.2022.101629},\n\tabstract = {Objective\nEpendymin-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.\nMethods\nEPDR1 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.\nResults\nEPDR1 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.\nConclusion\nThese 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.},\n\tlanguage = {en},\n\turldate = {2022-12-22},\n\tjournal = {Molecular Metabolism},\n\tauthor = {Cataldo, Luis Rodrigo and Gao, Qian and Argemi-Muntadas, Lidia and Hodek, Ondrej and Cowan, Elaine and Hladkou, Sergey and Gheibi, Sevda and Spégel, Peter and Prasad, Rashmi B. and Eliasson, Lena and Scheele, Camilla and Fex, Malin and Mulder, Hindrik and Moritz, Thomas},\n\tmonth = dec,\n\tyear = {2022},\n\tkeywords = {Beta cells, Insulin secretion, Lactate, Mitochondrial metabolism, TCA cycle, Type 2 diabetes},\n\tpages = {101629},\n}\n\n","author_short":["Cataldo, L. R.","Gao, Q.","Argemi-Muntadas, L.","Hodek, O.","Cowan, E.","Hladkou, S.","Gheibi, S.","Spégel, P.","Prasad, R. B.","Eliasson, L.","Scheele, C.","Fex, M.","Mulder, H.","Moritz, T."],"key":"cataldo_human_2022","id":"cataldo_human_2022","bibbaseid":"cataldo-gao-argemimuntadas-hodek-cowan-hladkou-gheibi-spgel-etal-thehumanbatokineepdr1regulatescellmetabolismandfunction-2022","role":"author","urls":{"Paper":"https://www.sciencedirect.com/science/article/pii/S2212877822001983"},"keyword":["Beta cells","Insulin secretion","Lactate","Mitochondrial metabolism","TCA cycle","Type 2 diabetes"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/zotero/upscpub","dataSources":["9cGcv2t8pRzC92kzs"],"keywords":["beta cells","insulin secretion","lactate","mitochondrial metabolism","tca cycle","type 2 diabetes"],"search_terms":["human","batokine","epdr1","regulates","cell","metabolism","function","cataldo","gao","argemi-muntadas","hodek","cowan","hladkou","gheibi","spégel","prasad","eliasson","scheele","fex","mulder","moritz"],"title":"The human batokine EPDR1 regulates β-cell metabolism and function","year":2022}