Loading...
Please wait, while we are loading the content...
Similar Documents
Important role of phosphodiesterase 3B for the stimulatory action of cAMP on pancreatic beta-cell exocytosis and release of insulin.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Härndahl, Linda Jing, X. F. Ivarsson, Rosita Degerman, Eva Ahrén, Bo Manganiello, Vincent C. Renström, Erik Holst, Lena Stenson |
| Copyright Year | 2002 |
| Abstract | Cyclic AMP potentiates glucose-stimulated insulin release and mediates the stimulatory effects of hormones such as glucagon-like peptide 1 (GLP-1) on pancreatic beta-cells. By inhibition of cAMP-degrading phosphodiesterase (PDE) and, in particular, selective inhibition of PDE3 activity, stimulatory effects on insulin secretion have been observed. Molecular and functional information on beta-cell PDE3 is, however, scarce. To provide such information, we have studied the specific effects of the PDE3B isoform by adenovirus-mediated overexpression. In rat islets and rat insulinoma cells, approximate 10-fold overexpression of PDE3B was accompanied by a 6-8-fold increase in membrane-associated PDE3B activity. The cAMP concentration was significantly lowered in transduced cells (INS-1(832/13)), and insulin secretion in response to stimulation with high glucose (11.1 mm) was reduced by 40% (islets) and 50% (INS-1). Further, the ability of GLP-1 (100 nm) to augment glucose-stimulated insulin secretion was inhibited by approximately 30% (islets) and 70% (INS-1). Accordingly, when stimulating with cAMP, a substantial decrease (65%) in exocytotic capacity was demonstrated in patch-clamped single beta-cells. In untransduced insulinoma cells, application of the PDE3-selective inhibitor OPC3911 (10 microm) was shown to increase glucose-stimulated insulin release as well as cAMP-enhanced exocytosis. The findings suggest a significant role of PDE3B as an important regulator of insulin secretory processes. |
| Starting Page | 1 |
| Ending Page | 7 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jbc.org/content/277/40/37446.full.pdf |
| PubMed reference number | 12169692v1 |
| Volume Number | 277 |
| Issue Number | 40 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 8-chloro-cyclic adenosine monophosphate Cell secretion Chronic Lymphocytic Leukemia Cyclic AMP Exocytosis FOXM1 wt Allele GCG gene Glucagon-Like Peptide Receptors Glucagon-Like Peptides Glucose PDE3B gene Rat Insulinoma Secretory Pathway Stimulation (motivation) Tissue membrane insulin secretion |
| Content Type | Text |
| Resource Type | Article |
