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Cyclic nucleotide phosphodiesterases in pancreatic islets

Pyne, N J and Furman, B L (2003) Cyclic nucleotide phosphodiesterases in pancreatic islets. Diabetologia, 46 (9). pp. 1179-1189. ISSN 0012-186X

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Abstract

Cyclic nucleotide phosphodiesterases (PDEs) comprise a family of enzymes (PDE1-PDE11) which hydrolyse cyclic AMP and cyclic GMP to their biologically inactive 5' derivatives. Cyclic AMP is an important physiological amplifier of glucose-induced insulin secretion. As PDEs are the only known mechanism for inactivating cyclic nucleotides, it is important to characterise the PDEs present in the pancreatic islet beta cells. Several studies have shown pancreatic islets or beta cells to contain PDE1C, PDE3B and PDE4, with some evidence for PDE10A. Most evidence suggests that PDE3B is the most important in relation to the regulation of insulin release, although PDE1C could have a role. PDE3-selective inhibitors augment glucose-induced insulin secretion. In contrast, activation of beta-cell PDE3B could mediate the inhibitory effect of IGF-1 and leptin on insulin secretion. In vivo, although PDE3 inhibitors augment glucose-induced insulin secretion, concomitant inhibition of PDE3B in liver and adipose tissue induce insulin resistance and PDE3 inhibitors do not induce hypoglycaemia. The development of PDE3 inhibitors as anti-diabetic agents would require differentiation between PDE3B in the beta cell and that in hepatocytes and adipocytes. Through their effects in regulating beta-cell cyclic nucleotide concentrations, PDEs could modulate beta-cell growth, differentiation and survival; some work has shown that selective inhibition of PDE4 prevents diabetes in NOD mice and that selective PDE3 inhibition blocks cytokine-induced nitric oxide production in islet cells. Further work is required to understand the mechanism of regulation and role of the various PDEs in islet-cell function and to validate them as targets for drugs to treat and prevent diabetes.

Item type: Article
ID code: 34958
Keywords: 3',5'-Cyclic-AMP Phosphodiesterases, 3',5'-Cyclic-GMP Phosphodiesterases, Animals, Cyclic AMP, Cyclic GMP, Cyclic Nucleotide Phosphodiesterases, Type 1, Humans, Islets of Langerhans, Isoenzymes, Therapeutics. Pharmacology, Internal Medicine, Endocrinology, Diabetes and Metabolism
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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Depositing user: Pure Administrator
Date Deposited: 15 Nov 2011 14:48
Last modified: 01 Oct 2014 16:40
URI: http://strathprints.strath.ac.uk/id/eprint/34958

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