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RNA sequencing unra...
RNA sequencing unravels novel L cell constituents and mechanisms of GLP-1 secretion in human gastric bypass-operated intestine
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- Miskelly, Michael G. (författare)
- Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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- Lindqvist, Andreas (författare)
- Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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- Piccinin, Elena (författare)
- Department of Translational Biomedicine and Neuroscience, University of Bari 'Aldo Moro', Bari, Italy; Department of Interdisciplinary Medicine, University of Bari 'Aldo Moro', Bari, Italy
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- Hamilton, Alexander (författare)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - molekylär metabolism,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Diabetes - Molecular Metabolism
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- Cowan, Elaine (författare)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Nergård, Bent-Johnny (författare)
- Aleris Obesitas, Lund, Sweden,Aleris Obesitas Skåne
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- Del Giudice, Rita (författare)
- Malmö University,Lund University,Lunds universitet,Malmö universitet,Biofilms Research Center for Biointerfaces,Institutionen för biomedicinsk vetenskap (BMV),Department of Experimental Medical Science, Lund University, Lund, Sweden,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups
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- Ngara, Mtakai (författare)
- Karolinska Institutet,Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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- Cataldo, Luis R. (författare)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,Novo Nordisk Foundation Centre for Basic Metabolic Research
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- Kryvokhyzha, Dmytro (författare)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Volkov, Petr (författare)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups
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- Engelking, Luke (författare)
- Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA
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- Artner, Isabella (författare)
- Lund University,Lunds universitet,Endokrin Celldifferentiering,Forskargrupper vid Lunds universitet,Bildbehandlingsplattformen,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Endocrine Cell Differentiation and Function,Lund University Research Groups,Imaging,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Lagerstedt, Jens O. (författare)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Eliasson, Lena (författare)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Ahlqvist, Emma (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Moschetta, Antonio (författare)
- Department of Interdisciplinary Medicine, University of Bari 'Aldo Moro', Bari, Italy; INBB National Institute for Biostructure and Biosystems, Rome, Italy
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- Hedenbro, Jan (författare)
- Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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- Wierup, Nils (författare)
- Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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(creator_code:org_t)
- Springer, 2024
- 2024
- Engelska.
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 67:2, s. 356-370
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Aims/hypothesis: Roux-en-Y gastric bypass surgery (RYGB) frequently results in remission of type 2 diabetes as well as exaggerated secretion of glucagon-like peptide-1 (GLP-1). Here, we assessed RYGB-induced transcriptomic alterations in the small intestine and investigated how they were related to the regulation of GLP-1 production and secretion in vitro and in vivo.Methods: Human jejunal samples taken perisurgically and 1 year post RYGB (n=13) were analysed by RNA-seq. Guided by bioinformatics analysis we targeted four genes involved in cholesterol biosynthesis, which we confirmed to be expressed in human L cells, for potential involvement in GLP-1 regulation using siRNAs in GLUTag and STC-1 cells. Gene expression analyses, GLP-1 secretion measurements, intracellular calcium imaging and RNA-seq were performed in vitro. OGTTs were performed in C57BL/6j and iScd1-/- mice and immunohistochemistry and gene expression analyses were performed ex vivo.Results: Gene Ontology (GO) analysis identified cholesterol biosynthesis as being most affected by RYGB. Silencing or chemical inhibition of stearoyl-CoA desaturase 1 (SCD1), a key enzyme in the synthesis of monounsaturated fatty acids, was found to reduce Gcg expression and secretion of GLP-1 by GLUTag and STC-1 cells. Scd1 knockdown also reduced intracellular Ca2+ signalling and membrane depolarisation. Furthermore, Scd1 mRNA expression was found to be regulated by NEFAs but not glucose. RNA-seq of SCD1 inhibitor-treated GLUTag cells identified altered expression of genes implicated in ATP generation and glycolysis. Finally, gene expression and immunohistochemical analysis of the jejunum of the intestine-specific Scd1 knockout mouse model, iScd1-/-, revealed a twofold higher L cell density and a twofold increase in Gcg mRNA expression.Conclusions/interpretation: RYGB caused robust alterations in the jejunal transcriptome, with genes involved in cholesterol biosynthesis being most affected. Our data highlight SCD as an RYGB-regulated L cell constituent that regulates the production and secretion of GLP-1.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- GLP-1
- Gastric bypass surgery
- Glucagon-like peptide-1
- Intestine
- Obesity
- RNA sequencing
- Remission
- SCD
- Stearoyl-CoA desaturase
- Type 2 diabetes
- Gastric bypass surgery
- GLP-1
- Glucagon-like peptide-1
- Intestine
- Obesity
- Remission
- RNA sequencing
- SCD
- Stearoyl-CoA desaturase
- Type 2 diabetes
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Miskelly, Michae ...
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Lindqvist, Andre ...
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Piccinin, Elena
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Hamilton, Alexan ...
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Cowan, Elaine
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Nergård, Bent-Jo ...
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visa fler...
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Del Giudice, Rit ...
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Ngara, Mtakai
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Cataldo, Luis R.
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Kryvokhyzha, Dmy ...
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Volkov, Petr
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Engelking, Luke
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Artner, Isabella
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Lagerstedt, Jens ...
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Eliasson, Lena
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Ahlqvist, Emma
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Moschetta, Anton ...
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Hedenbro, Jan
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Wierup, Nils
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
- Artiklar i publikationen
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Diabetologia
- Av lärosätet
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Malmö universitet
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Lunds universitet
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Karolinska Institutet