Long-term regulation of cyclic nucleotide phosphodiesterase type 3B and 4 in 3T3-L1 adipocytes

Oknianska, Alina; Zmuda-Trzebiatowska, Emilia; Manganiello, Vincent C.; Degerman, Eva

doi:10.1016/j.bbrc.2006.12.141

Cited by 15 publications

(15 citation statements)

References 35 publications

(46 reference statements)

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“…This is primarily associated with loss of PDE4A5; PDE3 does not significantly change. Long-term insulin treatment of adipocytes elicits an increase in PDE4D protein and activity with no measurable change in PDE4A, -4B, or -4C, all of which are expressed in these cells (281). PDE3B activity and protein are also increased under these conditions.…”

Section: Regulation Of Pde4 Isoenzymesmentioning

confidence: 93%

“…Insulin increases expression of activities and protein of both PDE3B and PDE4D in 3T3-L1 adipocytes (Table 1) (281), and PDE3B protein is downregulated in adipocytes from animal models of diabetes and obesity (89,371). Upregulation of PDE3B in response to insulin, dibutyryl cAMP, or dexamethasone involves actions of PI3K and a PKA-mediated increase in phospho-CREB (93,281), but the mechanism for this effect is not known. However, prolonged exposure of 3T3-L1 adipocytes to ␤-adrenergic agonists cause downregulation of PDE3B and upregulation of PDE4D (281).…”

Section: Regulation Of Pde3 Isoenzymesmentioning

confidence: 99%

“…Many studies have addressed control of expression of PDE4 isoenzymes, but results differ most likely due to species differences and/or the model used (2,154,261,368), and recent studies indicate differential regulation in expression of PDE4 isoenzymes (Table 2) (94, 281, 300). Elevation of cAMP is generally associated with upregulation of PDE4 isoenzymes (73,154,224,281,317,379), but in neonatal mouse cardiomyocytes, expression of the PDE4A10 promoter is decreased in response to PKA activation through elevation of cAMP that is controlled by ␤-adrenergic coupled AC activity (238). This downregulation is thought to involve the transcription factor ICER and supports selective expression of PDE4 isoenzymes.…”

Section: Regulation Of Pde4 Isoenzymesmentioning

confidence: 99%

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Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

Francis

Blount

Corbin

2011

Physiological Reviews

560

546

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The superfamily of cyclic nucleotide (cN) phosphodiesterases (PDEs) is comprised of 11 families of enzymes. PDEs break down cAMP and/or cGMP and are major determinants of cellular cN levels and, consequently, the actions of cN-signaling pathways. PDEs exhibit a range of catalytic efficiencies for breakdown of cAMP and/or cGMP and are regulated by myriad processes including phosphorylation, cN binding to allosteric GAF domains, changes in expression levels, interaction with regulatory or anchoring proteins, and reversible translocation among subcellular compartments. Selective PDE inhibitors are currently in clinical use for treatment of erectile dysfunction, pulmonary hypertension, intermittent claudication, and chronic pulmonary obstructive disease; many new inhibitors are being developed for treatment of these and other maladies. Recently reported x-ray crystallographic structures have defined features that provide for specificity for cAMP or cGMP in PDE catalytic sites or their GAF domains, as well as mechanisms involved in catalysis, oligomerization, autoinhibition, and interactions with inhibitors. In addition, major advances have been made in understanding the physiological impact and the biochemical basis for selective localization and/or recruitment of specific PDE isoenzymes to particular subcellular compartments. The many recent advances in understanding PDE structures, functions, and physiological actions are discussed in this review.

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Section: Regulation Of Pde4 Isoenzymesmentioning

confidence: 93%

Section: Regulation Of Pde3 Isoenzymesmentioning

confidence: 99%

Section: Regulation Of Pde4 Isoenzymesmentioning

confidence: 99%

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Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

Francis

Blount

Corbin

2011

Physiological Reviews

560

546

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“…Several PDE subtypes and isoforms, including PDE1 [7], PDE3B [8,9], PDE4 [7] and PDE8B [7,10], are known to mediate insulin secretion by pancreatic islets and/or beta cells. Through a feedback mechanism, insulin can reduce intracellular cAMP levels via activation of PDEs either by phosphorylation [11,12] or in the longer term by regulating their protein levels [13,14].…”

Section: Introductionmentioning

confidence: 99%

RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice

Zhai

Yang

et al. 2016

Diabetologia

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Aims/hypothesis CUG-binding protein 1 (CUGBP1) is a multifunctional RNA-binding protein that regulates RNA processing at several stages including translation, deadenylation and alternative splicing, as well as RNA stability. Recent studies indicate that CUGBP1 may play a role in metabolic disorders. Our objective was to examine its role in endocrine pancreas function through gain-and loss-of-function experiments and to further decipher the underlying molecular mechanisms. Methods A mouse model in which type 2 diabetes was induced by a high-fat diet (HFD; 60% energy from fat) and mice on a standard chow diet (10% energy from fat) were compared. Pancreas-specific CUGBP1 overexpression and knockdown mice were generated. Different lengths of the phosphodiesterase subtype 3B (PDE3B) 3′ untranslated region (UTR) were cloned for luciferase reporter analysis. Purified CUGBP1 protein was used for gel shift experiments.Results CUGBP1 is present in rodent islets and in beta cell lines; it is overexpressed in the islets of diabetic mice. Compared with control mice, the plasma insulin level after a glucose load was significantly lower and glucose clearance was greatly delayed in mice with pancreas-specific CUGBP1 overexpression; the opposite results were obtained upon pancreas-specific CUGBP1 knockdown. Glucose-and glucagon-like peptide1 (GLP-1)-stimulated insulin secretion was significantly attenuated in mouse islets upon CUGBP1 overexpression. This was associated with a strong decrease in intracellular cAMP levels, pointing to a potential role for cAMP PDEs. CUGBP1 overexpression had no effect on the mRNA levels of PDE1A, 1C, 2A, 3A, 4A, 4B, 4D, 7A and 8B subtypes, but resulted in increased PDE3B expression. CUGBP1 was found to directly bind to a specific ATTTGTT sequence residing in the 3′ UTR of PDE3B and stabilised PDE3B mRNA. In the presence of the PDE3 inhibitor cilostamide, glucose-and GLP-1-stimulated insulin secretion was no longer reduced by CUGBP1 overexpression. Similar to CUGBP1, PDE3B was overexpressed in the islets of diabetic mice. Conclusions/interpretation We conclude that CUGBP1 is a critical regulator of insulin secretion via activating PDE3B. Repressing this protein might provide a potential strategy for treating type 2 diabetes.

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“…The effect of insulin on lipolysis is attributed to the stimulation of activity and/or the expression of cyclic nucleotide phosphodiesterases 3B and 4 (15)(16)(17), which decrease intracellular levels of cAMP and reverse the stimulatory effect of cAMP-dependent protein kinase on lipolysis (5). In parallel, insulin may suppress lipolysis in a cAMP-independent fashion by stimulating protein phosphatase 1 and by promoting re-esterification of fatty acids (reviewed in Ref.…”

mentioning

confidence: 99%

FoxO1 Controls Insulin-dependent Adipose Triglyceride Lipase (ATGL) Expression and Lipolysis in Adipocytes

Chakrabarti

Kandror

2009

Journal of Biological Chemistry

187

169

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FoxO1 represents a central regulator of metabolism in several cell types. Although FoxO1 is abundant in adipocytes, its biological functions in these cells remain largely unknown. We show here that the promotor region of the rate-limiting lipolytic enzyme, adipose triglyceride lipase (ATGL), has two FoxO1-binding sites, and co-transfection with wild type and unphosphorylated FoxO1 mutant activates the expression of luciferase driven by the ATGL promotor. In 3T3-L1 adipocytes, insulin controls nucleo-cytoplasmic shuttling of FoxO1 and regulates its interaction with endogenous ATGL promotors. Knockdown of FoxO1 in 3T3-L1 adipocytes decreases the expression of ATGL and attenuates basal and isoproterenol-stimulated lipolysis. Infection of mouse embryonic fibroblasts with FoxO1-encoding lentivirus increases ATGL expression and renders it sensitive to regulation by insulin. Thus, FoxO1 may play an important role in the regulation of lipolysis in adipocytes by controlling the expression of ATGL.One of the key physiological functions of insulin in the mammalian organism is to inhibit lipolysis and to promote accumulation and storage of triglycerides in fat tissue. Control of lipolysis plays an important role in energy partitioning and balance and maintains the size of fat depots in the body. In patients with insulin resistance and type 2 diabetes, insulin cannot suppress high levels of free fatty acids (FFA) 2 in the bloodstream (1) so that the availability of FFA exceeds the energy requirements of the body. As a result, FFA are accumulated in the form of lipids in non-adipose peripheral tissues, such as liver and skeletal muscle, aggravating insulin resistance and causing multiple hazardous metabolic effects (2, 3). In addition, excess of FFA may lead to overproduction of VLDL in the liver and predispose the organism to cardiovascular disease.The complete hydrolysis of triglycerides to glycerol and FFA is performed jointly by tri-, di-, and monoacylglyceride lipases (4, 5). Recently discovered adipose triglyceride lipase ATGL (6 -8) is responsible for the bulk of triacylglycerol hydrolase activity in cells and has low affinity to di-and monoacylglycerides (4, 5). Importantly, ATGL is now considered the rate-limiting lipolytic enzyme in mammals (9), flies (10), and yeast (11). The major diacylglyceride lipase in adipocytes is hormone-sensitive lipase, or HSL (5). ATGL-and HSL-mediated hydrolase activity is controlled by catecholamines primarily via the cAMP-mediated-phosphorylation of perilipin (12, 13), the major lipid droplet-forming protein in adipocytes (14). Monoacylglyceride lipase in adipocytes is believed to be hormone-independent (4).The effect of insulin on lipolysis is attributed to the stimulation of activity and/or the expression of cyclic nucleotide phosphodiesterases 3B and 4 (15-17), which decrease intracellular levels of cAMP and reverse the stimulatory effect of cAMP-dependent protein kinase on lipolysis (5). In parallel, insulin may suppress lipolysis in a cAMP-independent fashion by stimulating pro...

show abstract

Long-term regulation of cyclic nucleotide phosphodiesterase type 3B and 4 in 3T3-L1 adipocytes

Cited by 15 publications

References 35 publications

Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice

FoxO1 Controls Insulin-dependent Adipose Triglyceride Lipase (ATGL) Expression and Lipolysis in Adipocytes

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