9 research outputs found
Expression and Regulation of Cyclic Nucleotide Phosphodiesterases in Human and Rat Pancreatic Islets
As shown by transgenic mouse models and by using phosphodiesterase 3 (PDE3) inhibitors, PDE3B has an important role in the regulation of insulin secretion in pancreatic β-cells. However, very little is known about the regulation of the enzyme. Here, we show that PDE3B is activated in response to high glucose, insulin and cAMP elevation in rat pancreatic islets and INS-1 (832/13) cells. Activation by glucose was not affected by the presence of diazoxide. PDE3B activation was coupled to an increase as well as a decrease in total phosphorylation of the enzyme. In addition to PDE3B, several other PDEs were detected in human pancreatic islets: PDE1, PDE3, PDE4C, PDE7A, PDE8A and PDE10A. We conclude that PDE3B is activated in response to agents relevant for β-cell function and that activation is linked to increased as well as decreased phosphorylation of the enzyme. Moreover, we conclude that several PDEs are present in human pancreatic islets
Structure of Protein Tyrosine Phosphatase 1B in Complex with Inhibitors Bearing Two Phosphotyrosine Mimetics
Alterations in cyclic nucleotide phosphodiesterase activities in omental and subcutaneous adipose tissues in human obesity
Induction of miR-132 and miR-212 Expression by Glucagon-Like Peptide 1 (GLP-1) in Rodent and Human Pancreatic β-Cells
Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion
Adenylyl cyclase 8 is central to glucagon-like peptide 1 signalling and effects of chronically elevated glucose in rat and human pancreatic beta cells
RNA-Seq Analysis of Abdominal Fat in Genetically Fat and Lean Chickens Highlights a Divergence in Expression of Genes Controlling Adiposity, Hemostasis, and Lipid Metabolism
Assays for Insulin and Insulin-Like Signal Transduction Based on Adipocytes, Hepatocytes, and Myocytes
After having established insulin-like activity of compounds/drug candidates in primary or cultured adipose, muscle, and liver cells or tissues with one or several of the metabolic assays described above (see K.6.1 and K.6.2), it is often useful to elucidate the molecular mode of action of these compounds/drug candidates for further characterization and optimization, in particular regarding selectivity and potency. For this, detailed knowledge in the molecular mechanisms of the insulin signal transduction cascade as well as of cross-talking insulin-like signaling pathways as well as the availability of appropriate reliable and robust cell-free and cell-based assays reflecting these events is required. The following view results from the current experimental findings but, due to limitations in space and rapid progress still made in this area, has to be considered as simplified and temporary, only