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The MafA-target gen...
The MafA-target gene PPP1R1A regulates GLP1R-mediated amplification of glucose-stimulated insulin secretion in β-cells
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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
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- Vishnu, Neelanjan (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Singh, Tania (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Bertonnier-Brouty, Ludivine (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Endokrin Celldifferentiering,Forskargrupper vid Lunds universitet,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Endocrine Cell Differentiation and Function,Lund University Research Groups
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- Bsharat, Sara (author)
- Lund University,Lunds universitet,Endokrin Celldifferentiering,Forskargrupper vid Lunds universitet,Endocrine Cell Differentiation and Function,Lund University Research Groups
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- Luan, Cheng (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Renström, Erik (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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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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- 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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- Artner, Isabella (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Endokrin Celldifferentiering,Forskargrupper vid Lunds universitet,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Endocrine Cell Differentiation and Function,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Metabolism: Clinical and Experimental. - : Elsevier BV. - 1532-8600.
- Related links:
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Abstract
Subject headings
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- The amplification of glucose-stimulated insulin secretion (GSIS) through incretin signaling is critical for maintaining physiological glucose levels. Incretins, like glucagon-like peptide 1 (GLP1), are a target of type 2 diabetes drugs aiming to enhance insulin secretion. Here we show that the protein phosphatase 1 inhibitor protein 1A (PPP1R1A), is expressed in β-cells and that its expression is reduced in dysfunctional β-cells lacking MafA and upon acute MafA knock down. MafA is a central regulator of GSIS and β-cell function. We observed a strong correlation of MAFA and PPP1R1A mRNA levels in human islets, moreover, PPP1R1A mRNA levels were reduced in type 2 diabetic islets and positively correlated with GLP1-mediated GSIS amplification. PPP1R1A silencing in β-cell lines impaired GSIS amplification, PKA-target protein phosphorylation, mitochondrial coupling efficiency and also the expression of critical β-cell marker genes like MafA, Pdx1, NeuroD1 and Pax6. Our results demonstrate that the β-cell transcription factor MafA is required for PPP1R1A expression and that reduced β-cell PPP1R1A levels impaired β-cell function and contributed to β-cell dedifferentiation during type 2 diabetes. Loss of PPP1R1A in type 2 diabetic β-cells may explains the unresponsiveness of type 2 diabetic patients to GLP1R-based treatments.
Subject headings
- 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 -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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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Vishnu, Neelanja ...
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Singh, Tania
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Bertonnier-Brout ...
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Bsharat, Sara
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Luan, Cheng
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show more...
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Renström, Erik
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Prasad, Rashmi B
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Fex, Malin
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Mulder, Hindrik
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Artner, Isabella
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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 Basic Medicine
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and Cell and Molecul ...
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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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Metabolism: Clin ...
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Metabolism
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Lund University