| 1. |
- Berger, Karin, et al.
(författare)
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Phosphodiesterase 3B is localized in caveolae and smooth ER in mouse hepatocytes and is important in the regulation of glucose and lipid metabolism.
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of signal transduction processes mediated by cAMP and cGMP. One PDE family member, PDE3B, plays an important role in the regulation of a variety of metabolic processes such as lipolysis and insulin secretion. In this study, the cellular localization and the role of PDE3B in the regulation of triglyceride, cholesterol and glucose metabolism in hepatocytes were investigated. PDE3B was identified in caveolae, specific regions in the plasma membrane, and smooth endoplasmic reticulum. In caveolin-1 knock out mice, which lack caveolae, the amount of PDE3B protein and activity were reduced indicating a role of caveolin-1/caveolae in the stabilization of enzyme protein. Hepatocytes from PDE3B knock out mice displayed increased glucose, triglyceride and cholesterol levels, which was associated with increased expression of gluconeogenic and lipogenic genes/enzymes including, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor gamma, sterol regulatory element-binding protein 1c and hydroxyl-3-methylglutaryl coenzyme A reductase. In conclusion, hepatocyte PDE3B is localized in caveolae and smooth endoplasmic reticulum and plays important roles in the regulation of glucose, triglyceride and cholesterol metabolism. Dysregulation of PDE3B could have a role in the development of fatty liver, a condition highly relevant in the context of type 2 diabetes.
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| 2. |
- Lindqvist, Andreas, et al.
(författare)
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Enterostatin up-regulates the expression of the beta-subunit of F(1)F(o)-ATPase in the plasma membrane of INS-1 cells.
- 2008
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Ingår i: Nutritional Neuroscience. - 1476-8305. ; 11:2, s. 55-60
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to high-fat diet easily promotes overeating while at the same time disrupting insulin secretion and islet function. Enterostatin is a peptide which is secreted from the pancreas in response to high-fat feeding and has been shown to inhibit fat intake as well as insulin secretion in experimental animal models. Until recently, there was no known receptor for enterostatin. In 2002, Berger and co-workers found enterostatin to target the beta-subunit of the F(1)-ATPase in rat brain membranes as well as in a clonal beta-cell line (INS-1). In this study, we found the beta-subunit of F(1)-ATPase to be ectopically expressed in the plasma membrane of INS-1 cells using both immunohistochemistry and Western blotting. Incubation with enterostatin for 60 min resulted in a 3.5-fold increase of the protein expression of the beta-subunit of F(1)-ATPase in the plasma membrane. Furthermore, we found ATP to be able to displace the binding of enterostatin to purified bovine F(1)-ATPase. This reported targeting of enterostatin to the beta-subunit of F(1)-ATPase in insulin cells may provide a link between high-fat intake and islet function.
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