Phosphodiesterase 3 and 4 comprise the major cAMP metabolizing enzymes responsible for insulin secretion in INS-1 (832/13) cells and rat islets.

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Phosphodiesterase 3 and 4 comprise the major cAMP metabolizing enzymes responsible for insulin secretion in INS-1 (832/13) cells and rat islets.

Waddleton, D., Wu, W., Feng, Y., Thompson, C., Wu, M., Zhou, Y.P., Howard, A., Thornberry, N., Li, J., Mancini, J.A.

Journal		Biochemical Pharmacology
Species
Analytes Measured		Insulin
Matrix Tested		INS-1 cell culture supernatants

Year		2008
Volume		76
Page Numbers		884-93
Application		Metabolic

Abstract

cAMP is a key modulator for glucose-dependent insulin secretion (GDIS). Members of the phosphodiesterase (PDEs) gene family regulate intracellular levels of cAMP by hydrolyzing cAMP to the corresponding inactive 5'AMP derivative. These studies examined the expression and function of all 18 cAMP-specific PDEs in the rat insulinoma derived INS-1 (832/13) cell and isolated rat islets using quantitative PCR and siRNA-mediated gene-specific knockdown. PDE1C, PDE3B, PDE4C, PDE8B, PDE10A, and PDE11A were significantly expressed in rat islets and INS-1 (832/13) cells at the mRNA level. PDE1C, PDE10A and PDE11A were also expressed in brain, along with PDE3B, PDE4C and PDE8B which were also highly expressed in liver, and PDE3B was present in adipose tissue and PDE4C in skeletal muscle. siRNA mediated knockdown of PDE1C, PDE3B, PDE8B and PDE4C, but not PDE10A and PDE11A, significantly enhanced GDIS in rat INS-1 (832/13) cells. Also, selective inhibitors of PDE3 (trequinsin) and PDE4 (roflumilast and L-826,141) significantly augmented GDIS in both INS-1 (832/13) cells and rat islets. The combination of PDE3 and PDE4 selective inhibitors demonstrate that these enzymes comprise a significant proportion of the cAMP metabolizing activity in INS-1 cells and rat islets.

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U-PLEX Metabolic Hormones Combo 1 (rat) C-Peptide, Ghrelin (active), GLP-1 (active), Glucagon, Insulin, Leptin, PYY (total) \| Rat Multiplex
U-PLEX Metabolic Hormones Combo 1 (mouse) C-Peptide, Ghrelin (active), GLP-1 (active), Glucagon, IL-6, Insulin, Leptin, MCP-1, PYY (total), TNF-α \| Mouse Multiplex
U-PLEX Metabolic Group 1 (mouse) 58-Plex BAFF, BCA-1/BLC, BDNF, CD40/TNFRSF5, C-Peptide, Eotaxin, EPO, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, IFN-α, IFN-β, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, Insulin, IP-10, KC/GRO, Leptin, MCP-1, MCP-5/CCL12, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α, MMP-9 (total), PYY (total), RANTES, TARC, TNF-α, VEGF-A \| Mouse Multiplex
U-PLEX Metabolic Combo 1 (rat) BDNF, C-Peptide, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) \| Rat Multiplex
U-PLEX Metabolic Combo 1 (mouse) BAFF, BDNF, C-Peptide, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) \| Mouse Multiplex
U-PLEX Metabolic 3-Plex Combo 2 (rat) GLP-1 (active), Glucagon, Insulin \| Rat Multiplex
U-PLEX Metabolic 3-Plex Combo 2 (mouse) GLP-1 (active), Glucagon, Insulin \| Mouse Multiplex
U-PLEX Metabolic 2-Plex Combo 2 (rat) Glucagon, Insulin \| Rat Multiplex
U-PLEX Metabolic 2-Plex Combo 2 (mouse) Glucagon, Insulin \| Mouse Multiplex
U-PLEX Metabolic 2-Plex Combo 1 (rat) Insulin, Leptin \| Rat Multiplex
U-PLEX Metabolic 2-Plex Combo 1 (mouse) Insulin, Leptin \| Mouse Multiplex
U-PLEX Gut Hormone Combo 1 (mouse) Ghrelin (active), GLP-1 (active), Glucagon, Insulin, Leptin, PYY (total) \| Mouse Multiplex
U-PLEX Adipokine Combo 1 (mouse) BDNF, IL-1β, IL-6, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Mouse Multiplex
U-PLEX Obesity Combo 2 (rat) C-Peptide, Ghrelin (total), GLP-1 (total), Insulin, Leptin, PYY (total) \| Rat Multiplex
U-PLEX Obesity Combo 2 (mouse) C-Peptide, Ghrelin (total), GLP-1 (total), Insulin, Leptin, PYY (total) \| Mouse Multiplex
U-PLEX Metabolic 4-Plex Combo 1 (human) GLP-1 (active), Glucagon, Insulin, Leptin \| Human Multiplex
U-PLEX Metabolic 3-Plex Combo 1 (human) GLP-1 (active), Glucagon, Insulin \| Human Multiplex
U-PLEX Metabolic 2-Plex Combo 1 (human) Insulin, Leptin \| Human Multiplex
U-PLEX Metabolic Group 1 (human) 87-Plex BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Custom Metabolic Group 1 (human) Assays BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Human Insulin Antibody Set Insulin \| Human
U-PLEX Metabolic Combo 1 (human) BAFF, BDNF, β-NGF, C-Peptide, FGF-21, FGF-23, FSH, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, Luteinizing Hormone (LH), PP, Proinsulin, PYY (total) \| Human Multiplex
U-PLEX Diabetes Combo 2 (human) C-Peptide, GIP (total), GLP-1 (active), Glucagon, Insulin, Leptin, PYY (total) \| Human Multiplex
U-PLEX Adipokine Combo 1 (human) BDNF, β-NGF, IL-1β, IL-6, IL-8, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Human Multiplex
U-PLEX Obesity Combo 2 (human) C-Peptide, FGF-23, Ghrelin (total), GLP-1 (total), Insulin, Leptin, PYY (total) \| Human Multiplex
Mouse Metabolic Kit Insulin, Leptin \| Mouse Multiplex
Mouse/Rat Insulin Kit Insulin \| Mouse, Rat Singleplex
Human Insulin Kit Insulin \| Human Singleplex

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Phosphodiesterase 3 and 4 comprise the major cAMP metabolizing enzymes responsible for insulin secretion in INS-1 (832/13) cells and rat islets.

Abstract

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