The Calcium/Calmodulin-dependent Phosphodiesterase PDE1C Down-regulates Glucose-induced Insulin Secretion

Han, Ping; Werber, John; Surana, Manju; Fleischer, Norman; Michaeli, Tamar

doi:10.1074/jbc.274.32.22337

Cited by 87 publications

(92 citation statements)

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“…25 l/100 islets were used for Ad␤-gal infection (lanes 3-4), and 25, 50, 100, and 200 l/100 islets were used for AdPDE3B-infection (lanes 5-8) insulin release in islets and different clonal ␤-cells. It appears, however, that selective inhibition of PDE3, for instance by milrinone (15), Org 9935, SK&F 94836, and siguazodan (12,16), at micromolar concentrations augments glucose-stimulated insulin secretion in rat islets (12,15) and rat-derived BRIN-BD11 cells (16). Here, we decided to evaluate the effect of the PDE3-selective inhibitor OPC3911 on exocytosis of insulin granules in INS-1(832/13) cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The availability of family-selective PDE inhibitors has facilitated understanding of the roles of specific PDEs in different tissues. With the use of such inhibitors, activities belonging to, at least, PDE families 1, 3, and 4 have been recognized in ␤-cells (12)(13)(14)(15)(16). The relative contribution of these PDEs to secretory events is not known, although in isolated rat islets inhibition of PDE1 (15) and PDE3 (12,15), and to a lesser extent inhibition of PDE4 (15), has been reported to augment insulin release.…”

mentioning

confidence: 99%

“…With the use of such inhibitors, activities belonging to, at least, PDE families 1, 3, and 4 have been recognized in ␤-cells (12)(13)(14)(15)(16). The relative contribution of these PDEs to secretory events is not known, although in isolated rat islets inhibition of PDE1 (15) and PDE3 (12,15), and to a lesser extent inhibition of PDE4 (15), has been reported to augment insulin release. Di-verging results have been obtained by use of insulinoma cells; in BRIN-BD11 cells, inhibition of PDE3 and 4, but not PDE1 (16), and in ␤-TC3 cells inhibition of PDE4, but not PDE3 (15), seems to stimulate insulin secretion.…”

mentioning

confidence: 99%

“…The relative contribution of these PDEs to secretory events is not known, although in isolated rat islets inhibition of PDE1 (15) and PDE3 (12,15), and to a lesser extent inhibition of PDE4 (15), has been reported to augment insulin release. Di-verging results have been obtained by use of insulinoma cells; in BRIN-BD11 cells, inhibition of PDE3 and 4, but not PDE1 (16), and in ␤-TC3 cells inhibition of PDE4, but not PDE3 (15), seems to stimulate insulin secretion. Data from in vivo experiments indicate that PDE3 inhibitors act as insulin secretagogues in rodents (13,17).…”

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confidence: 99%

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Important Role of Phosphodiesterase 3B for the Stimulatory Action of cAMP on Pancreatic β-Cell Exocytosis and Release of Insulin

Härndahl¹,

Jing²,

Ivarsson³

et al. 2002

Journal of Biological Chemistry

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Cyclic AMP potentiates glucose-stimulated insulin release and mediates the stimulatory effects of hormones such as glucagon-like peptide 1 (GLP-1) on pancreatic ␤-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 ␤-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 ϳ30% (islets) and 70% (INS-1). Accordingly, when stimulating with cAMP, a substantial decrease (65%) in exocytotic capacity was demonstrated in patch-clamped single ␤-cells. In untransduced insulinoma cells, application of the PDE3-selective inhibitor OPC3911 (10 M) 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.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Important Role of Phosphodiesterase 3B for the Stimulatory Action of cAMP on Pancreatic β-Cell Exocytosis and Release of Insulin

Härndahl¹,

Jing²,

Ivarsson³

et al. 2002

Journal of Biological Chemistry

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“…However, Han and colleagues have shown in isolated islets that inhibition of PDE1C but not PDE4 increased glucose-induced insulin secretion in a dose-dependent manner (Han et al, 1999). The combined inhibition of PDE1C, 3 and 4 had as potent an effect on augmentation of insulin secretion by glucose as non-specific inhibition by isobutylmethylxanthine (IBMX).…”

Section: Stimulation Of Camp Productionmentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

574

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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The role of the calmodulin‐dependent pathway in static magnetic field‐induced mechanotransduction

Yang

Lee

Chen

et al. 2009

Bioelectromagnetics

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While the effects of static magnetic fields (SMFs) on osteoblastic differentiation are well demonstrated, the mechanotransduction pathways of SMFs are still unclear. The aim of this study was to explore the role of calmodulin in the biophysical effects of SMFs on osteoblastic cells. MG63 cells were exposed to a 0.4 T SMF. The expression of phosphodiesterase RNA in the cytoplasm was tested using real-time polymerase chain reaction. The differentiation of the cells was assessed by detecting changes in alkaline phosphatase activity. The role of calmodulin antagonist W-7 was used to evaluate alterations in osteoblastic proliferation and differentiation after the SMF simulations. Our results showed that SMF exposure increased alkaline phosphatase activity and phosphodiesterase 1C gene expression in MG63 cells. Addition of W-7 significantly inhibited the SMF-induced cellular response. We suggest that one possible mechanism by which SMFs affects osteoblastic maturation is through a calmodulin-dependent mechanotransduction pathway.

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The Calcium/Calmodulin-dependent Phosphodiesterase PDE1C Down-regulates Glucose-induced Insulin Secretion

Cited by 87 publications

References 50 publications

Important Role of Phosphodiesterase 3B for the Stimulatory Action of cAMP on Pancreatic β-Cell Exocytosis and Release of Insulin

Important Role of Phosphodiesterase 3B for the Stimulatory Action of cAMP on Pancreatic β-Cell Exocytosis and Release of Insulin

Mechanisms of action of glucagon-like peptide 1 in the pancreas

The role of the calmodulin‐dependent pathway in static magnetic field‐induced mechanotransduction

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