{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:36:26Z","timestamp":1791326186501,"version":"4.3.1"},"reference-count":47,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,2,1]]},"abstract":"<jats:p>cAMP activates multiple signal pathways, crucial for the pancreatic \u03b2-cells function and survival and is a major potentiator of insulin release. A family of phosphodiesterases (PDEs) terminate the cAMP signals. We examined the expression of PDEs in rat \u03b2-cells and their role in the regulation of insulin response. Using RT-PCR and Western blot analyses, we identified PDE3A, PDE3B, PDE4B, PDE4D, and PDE8B in rat islets and in INS-1E cells and several possible splice variants of these PDEs. Specific depletion of PDE3A with small interfering (si) RNA (siPDE3A) led to a small (67%) increase in the insulin response to glucose in INS-1E cells but not rat islets. siPDE3A had no effect on the glucagon-like peptide-1 (10 nmol\/liter) potentiated insulin response in rat islets. Depletion in PDE8B levels in rat islets using similar technology (siPDE8B) increased insulin response to glucose by 70%, the potentiation being of similar magnitude during the first and second phase insulin release. The siPDE8B-potentiated insulin response was further increased by 23% when glucagon-like peptide-1 was included during the glucose stimulus. In conclusion, PDE8B is expressed in a small number of tissues unrelated to glucose or fat metabolism. We propose that PDE8B, an 3-isobutyl-1-methylxanthine-insensitive cAMP-specific phosphodiesterase, could prove a novel target for enhanced insulin response, affecting a specific pool of cAMP involved in the control of insulin granule trafficking and exocytosis. Finally, we discuss evidence for functional compartmentation of cAMP in pancreatic \u03b2-cells.<\/jats:p>","DOI":"10.1210\/en.2007-0968","type":"journal-article","created":{"date-parts":[[2007,11,9]],"date-time":"2007-11-09T01:25:41Z","timestamp":1194571541000},"page":"741-748","source":"Crossref","is-referenced-by-count":47,"title":["Diminished Phosphodiesterase-8B Potentiates Biphasic Insulin Response to Glucose"],"prefix":"10.1210","volume":"149","author":[{"given":"Avital","family":"Dov","sequence":"first","affiliation":[{"name":"Endocrinology and Metabolism Service, Department of Medicine, Hadassah, the Hebrew University Medical Center, 91120 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Abramovitch","sequence":"first","affiliation":[{"name":"Endocrinology and Metabolism Service, Department of Medicine, Hadassah, the Hebrew University Medical Center, 91120 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Warwar","sequence":"first","affiliation":[{"name":"Endocrinology and Metabolism Service, Department of Medicine, Hadassah, the Hebrew University Medical Center, 91120 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Nesher","sequence":"first","affiliation":[{"name":"Endocrinology and Metabolism Service, Department of Medicine, Hadassah, the Hebrew University Medical Center, 91120 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2007,11,8]]},"reference":[{"key":"2020071612231405900_R1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1006\/scdb.2000.0175","article-title":"Metabolic control of \u03b2-cell function.","volume":"11","author":"Deeney","year":"2000","journal-title":"Semin Cell Dev Biol"},{"key":"2020071612231405900_R2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0098-2997(01)00013-9","article-title":"Nutrient-secretion coupling in the pancreatic islet \u03b2-cell: recent advances.","volume":"22","author":"Rutter","year":"2001","journal-title":"Mol Aspects Med"},{"key":"2020071612231405900_R3","first-page":"898","article-title":"Modulation of cyclic nucleotides and cyclic nucleotide phosphodiesterases in pancreatic islet \u03b2-cells and intestinal L-cells as targets for treating diabetes mellitus.","volume":"7","author":"Furman","year":"2006","journal-title":"Curr Opin Investig Drugs"},{"key":"2020071612231405900_R4","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1211\/0022357044805","article-title":"Targeting \u03b2-cell cyclic 3\u20325\u2032 adenosine monophosphate for the development of novel drugs for treating type 2 diabetes mellitus. 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