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Beta-cell-targeted ...
Beta-cell-targeted overexpression of phosphodiesterase 3B in mice causes impaired insulin secretion, glucose intolerance, and deranged islet morphology.
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- Härndahl, Linda (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Wierup, Nils (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Enerbäck, Sven, 1958 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicinsk och fysiologisk kemi,Institute of Medical Biochemistry
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- Mulder, Hindrik (författare)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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Manganiello, Vincent C (författare)
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- Sundler, Frank (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
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- Degerman, Eva (författare)
- Lund University,Lunds universitet,Signaltransduktionsforskning,Forskargrupper vid Lunds universitet,Insulin Signal Transduction,Lund University Research Groups
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- Ahrén, Bo (författare)
- Lund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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Holst Stenson, Lena (författare)
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(creator_code:org_t)
- 2004
- 2004
- Engelska.
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Ingår i: The Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 279:15, s. 15214-22
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Abstract
Ämnesord
Stäng
- The second messenger cAMP mediates potentiation of glucose-stimulated insulin release. Use of inhibitors of cAMP-hydrolyzing phosphodiesterase (PDE) 3 and overexpression of PDE3B in vitro have demonstrated a regulatory role for this enzyme in insulin secretion. In this work, the physiological significance of PDE3B-mediated degradation of cAMP for the regulation of insulin secretion in vivo and glucose homeostasis was investigated in transgenic mice overexpressing PDE3B in pancreatic beta-cells. A 2-fold overexpression of PDE3B protein and activity blunted the insulin response to intravenous glucose, resulting in reduced glucose disposal. The effects were "dose"-dependent because mice overexpressing PDE3B 7-fold failed to increase insulin in response to glucose and hence exhibited pronounced glucose intolerance. Also, the insulin secretory response to intravenous glucagon-like peptide 1 was reduced in vivo. Similarly, islets stimulated in vitro exhibited reduced insulin secretory capacity in response to glucose and glucagon-like peptide 1. Perifusion experiments revealed that the reduction specifically affected the first phase of glucose-stimulated insulin secretion. Furthermore, morphological examinations demonstrated deranged islet cytoarchitecture. In conclusion, these results are consistent with an essential role for PDE3B in cAMP-mediated regulation of insulin release and glucose homeostasis.
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
- 3'
- 5'-Cyclic-Nucleotide Phosphodiesterase
- biosynthesis
- Animals
- Blotting
- Western
- Cyclic AMP
- metabolism
- DNA
- Complementary
- metabolism
- Dose-Response Relationship
- Drug
- Glucagon
- chemistry
- Glucagon-Like Peptide 1
- Glucose
- metabolism
- Immunohistochemistry
- Insulin
- metabolism
- secretion
- Islets of Langerhans
- cytology
- metabolism
- Mice
- Mice
- Inbred CBA
- Mice
- Transgenic
- Microscopy
- Fluorescence
- Peptide Fragments
- chemistry
- Protein Precursors
- chemistry
- Reverse Transcriptase Polymerase Chain Reaction
- Time Factors
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Härndahl, Linda
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Wierup, Nils
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Enerbäck, Sven, ...
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Mulder, Hindrik
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Manganiello, Vin ...
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Sundler, Frank
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visa fler...
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Degerman, Eva
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Ahrén, Bo
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Holst Stenson, L ...
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visa färre...
- Om ämnet
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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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The Journal of b ...
- Av lärosätet
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Göteborgs universitet
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Lunds universitet