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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

Beta-cell-targeted overexpression of phosphodiesterase 3B in mice causes impaired insulin secretion, glucose intolerance and deranged glucose morphology.


  • Linda Härndahl
  • Nils Wierup
  • Sven Enerbäck
  • Hindrik Mulder
  • Vincent C Manganiello
  • Frank Sundler
  • Eva Degerman
  • Bo Ahrén
  • Lena Stenson Holst

Summary, in English

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.


  • Department of Experimental Medical Science
  • Diabetes - Molecular Metabolism
  • Insulin Signal Transduction
  • Medicine, Lund

Publishing year







Journal of Biological Chemistry





Document type

Journal article




  • Cell and Molecular Biology



Research group

  • Diabetes - Molecular Metabolism
  • Insulin Signal Transduction


  • ISSN: 1083-351X