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Reduced Expression ...
Reduced Expression Level of Protein Phosphatase PPM1E Serves to Maintain Insulin Secretion in Type 2 Diabetes
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- Gheibi, Sevda (author)
- Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Diabetes - molekylär metabolism,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Diabetes - Molecular Metabolism
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- Cataldo, Luis Rodrigo (author)
- Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Diabetes - molekylär metabolism,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Diabetes - Molecular Metabolism,University of Copenhagen,Novo Nordisk Foundation Centre for Basic Metabolic Research
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- Hamilton, Alexander (author)
- Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Diabetes - öcellsexocytos,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Diabetes - Islet Cell Exocytosis,University of Copenhagen
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- Huang, Mi (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Kalamajski, Sebastian (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Fex, Malin (author)
- Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Diabetes - molekylär metabolism,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Diabetes - Molecular Metabolism
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- Mulder, Hindrik (author)
- Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Diabetes - molekylär metabolism,LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Diabetes - Molecular Metabolism
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(creator_code:org_t)
- 2023-01-20
- 2023
- English 12 s.
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In: Diabetes. - : American Diabetes Association. - 0012-1797. ; 72:4, s. 455-466
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Abstract
Subject headings
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- Reversible phosphorylation is an important regulatory mechanism. Regulation of protein phosphorylation in β-cells has been extensively investigated, but less is known about protein dephosphorylation. To understand the role of protein dephosphorylation in β-cells and type 2 diabetes (T2D), we first examined mRNA expression of the type 2C family (PP2C) of protein phosphatases in islets from T2D donors. Phosphatase expression overall was changed in T2D, and that of PPM1E was the most markedly downregulated. PPM1E expression correlated inversely with HbA1c. Silencing of PPM1E increased glucose-stimulated insulin secretion (GSIS) in INS-1 832/13 cells and/or islets from patients with T2D, whereas PPM1E overexpression decreased GSIS. Increased GSIS after PPM1E silencing was associated with decreased oxidative stress, elevated cytosolic Ca2+ levels and ATP to ADP ratio, increased hyperpo-larization of the inner mitochondrial membrane, and phosphorylation of CaMKII, AMPK, and acetyl-CoA car-boxylase. Silencing of PPM1E, however, did not change insulin content. Increased GSIS, cell viability, and activation of AMPK upon metformin treatment in β-cells were observed upon PPM1E silencing. Thus, protein de-phosphorylation via PPM1E abrogates GSIS. Conse-quently, reduced PPM1E expression in T2D may be a compensatory response of β-cells to uphold insulin secretion under metabolic duress. Targeting PPM1E in β-cells may thus represent a novel therapeutic strategy for treatment of T2D.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- art (subject category)
- ref (subject category)
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