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1. Inner ear is a target for insulin signaling and insulin resistance: evidence from mice and auditory HEI-OC1 cells.

Author

Pålbrink, Ann-Ki, Kopietz, Franziska, Morén, Björn, In 't Zandt, René, Kalinec, Federico, Stenkula, Karin, Göransson, Olga, Holm, Cecilia, Magnusson, Måns, and Degerman, Eva

Subjects
complication(s), ears, effects of insulin, insulin resistance, Clinical Sciences
Abstract

ObjectiveThe mechanisms underlying the association between diabetes and inner ear dysfunction are not known yet. The aim of the present study is to evaluate the impact of obesity/insulin resistance on inner ear fluid homeostasis in vivo, and to investigate whether the organ of Corti could be a target tissue for insulin signaling using auditory House Ear Institute-Organ of Corti 1 (HEI-OC1) cells as an in vitro model.MethodsHigh fat diet (HFD) fed C57BL/6J mice were used as a model to study the impact of insulin resistance on the inner ear. In one study, 12 C57BL/6J mice were fed either control diet or HFD and the size of the inner ear endolymphatic fluid compartment (EFC) was measured after 30 days using MRI and gadolinium contrast as a read-out. In another study, the size of the inner ear EFC was evaluated in eight C57BL/6J mice both before and after HFD feeding, with the same techniques. HEI-OC1 auditory cells were used as a model to investigate insulin signaling in organ of Corti cells.ResultsHFD feeding induced an expansion of the EFC in C57BL/6J mice, a hallmark of inner ear dysfunction. Insulin also induced phosphorylation of protein kinase B (PKB/Akt) at Ser473, in a PI3-kinase-dependent manner. The phosphorylation of PKB was inhibited by isoproterenol and IBMX, a general phosphodiesterase (PDE) inhibitor. PDE1B, PDE4D and the insulin-sensitive PDE3B were found expressed and catalytically active in HEI-OC1 cells. Insulin decreased and AICAR, an activator of AMP-activated protein kinase, increased the phosphorylation at the inhibitory Ser79 of acetyl-CoA carboxylase, the rate-limiting enzyme in de novo lipogenesis. Furthermore, the activity of hormone-sensitive lipase, the rate-limiting enzyme in lipolysis, was detected in HEI-OC1 cells.ConclusionsThe organ of Corti could be a target tissue for insulin action, and inner ear insulin resistance might contribute to the association between diabetes and inner ear dysfunction.

Published
2020

4. Salt-inducible kinase 2 and -3 are downregulated in adipose tissue from obese or insulin-resistant individuals: implications for insulin signalling and glucose uptake in human adipocytes

Author

Säll, Johanna, Pettersson, Annie M. L., Björk, Christel, Henriksson, Emma, Wasserstrom, Sebastian, Linder, Wilhelm, Zhou, Yuedan, Hansson, Ola, Andersson, Daniel P., Ekelund, Mikael, Degerman, Eva, Stenkula, Karin G., Laurencikiene, Jurga, and Göransson, Olga

Published
2017
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9. Increased whole body energy expenditure and protection against diet-induced obesity in Cyp8b1-deficient mice is accompanied by altered adipose tissue features

Author

Axling, Ulrika, Cavalera, Michele, Degerman, Eva, Gåfvels, Mats, Eggertsen, Gosta, and Holm, Cecilia

Subjects
brown adipocytes, insulin secretion, Fysiologi, white adipocytes, Physiology, glucose tolerance, Lipolysis, Endocrinology and Diabetes, Diet, High-Fat, Diseases of the endocrine glands. Clinical endocrinology, Mice, energy expenditure, Adipocytes, QP1-981, insulin sensitivity, Animals, Insulin, Steroid 12-alpha-Hydroxylase, Obesity, lipogenesis, Mice, Knockout, QH573-671, RC648-665, Lipid Metabolism, Bile acids, Mitochondria, Disease Models, Animal, Glucose, Adipose Tissue, Endokrinologi och diabetes, lipolysis, Disease Susceptibility, Insulin Resistance, Cytology, Energy Metabolism, Research Article, Research Paper
Abstract

The aim of this study was to elucidate mechanisms whereby bile acids exert beneficial metabolic effects, using the Cyp8b1−/- mouse as model. These mice are unable to synthesize cholic acid, resulting in increased synthesis of chenodeoxycholic acid and enlarged bile acid pool. Cyp8b1−/- mice were found to be protected against high-fat diet induced obesity. Bomb calorimetry measurements showed increased faecal energy output in Cyp8b1−/mice. Indirect calorimetry measurements demonstrated increased energy expenditure in Cyp8b1−/- mice. Meal tolerance tests revealed no differences in glucose disposal, but the insulin response was lower in Cyp8b1−/- mice. Intravenous glucose tolerance tests, as well as static incubations of isolated islets, showed no difference between the groups, whereas insulin tolerance tests demonstrated improved insulin sensitivity in Cyp8b1−/- mice. The genes encoding mitochondrial transcription factor A (TFAM) and type 2-iodothyronine deiodinase were upregulated in brown adipose tissue of Cyp8b1/- mice and Western blot analyses showed increased abundance of TFAM, and a trend towards increased abundance of UCP1. The upregulation of TFAM and UCP1 was accompanied by increased mitochondrial density, as shown by transmission electron microscopy. White adipocytes of Cyp8b1−/- mice exhibited increased responsiveness to both catecholamines and insulin in lipolysis experiments and increased insulin-stimulated lipogenesis. In conclusion, increased energy expenditure, mitochondrial density of brown adipocytes and faecal energy output may all contribute to the protection against diet-induced obesity of Cyp8b1−/- mice. Enhanced insulin sensitivity of Cyp8b1−/- mice is accompanied by increased hormonal responsiveness of white adipocytes.

Published
2020

18. Protein kinase B activity is required for the effects of insulin on lipid metabolism in adipocytes

Author

Berggreen, Christine, Gormand, Amelie, Omar, Bilal, Degerman, Eva, and Goransson, Olga

Subjects
Protein kinases -- Properties, Protein kinases -- Influence, Fat cells -- Properties, Lipid metabolism -- Research, Insulin -- Influence, Biological control systems -- Research, Biological sciences
Abstract

Protein kinase B (PKB) is known to mediate a number of biological responses to insulin and growth factors, its role in glucose uptake being one of the most extensively studied. In this work, we have employed a recently described allosteric inhibitor of PKB, Akti, to clarify the role of PKB in lipid metabolism in adipocytes--a subject that has received less attention. Pretreatment of primary rat and 3T3L1 adipocytes with Akti resulted in dose-dependent inhibition of PKB phosphorylation and activation in response to insulin, without affecting upstream insulin signaling [insulin receptor (IR), insulin receptor substrate ORS)] or the insulin-induced phosphoinositide 3-kinase (PI3K)-dependent activation of the ERK/p90 ribosomal kinase (RSK) pathway. PKB activity was required for the insulin-induced activation of phosphodiesterase 3B (PDE3B) and for the antilipolytic action of insulin. Moreover, inhibition of PKB activity resulted in a reduction in de novo lipid synthesis and in the ability of insulin to stimulate this process. The regulation of the rate-limiting lipogenic enzyme acetyl-CoA carboxylase (ACC) by insulin through dephosphorylation of S79, which is a target for AMP-activated protein kinase (AMPK), was dependent on the presence of active PKB. Finally, AMPK was shown to be phosphorylated by PKB on S485 in response to insulin, and this was associated with a reduction in AMPK activity. In summary, we propose that PKB is required for the positive effects of insulin on lipid storage and that regulation of PDE3B and AMPK by PKB is important for these effects. Akt; phosphodiesterase 3B; acetyl-coenzyme A carboxylase; adenosine 5'-monophosphate-activated protein kinase; lipogenesis

Published
2009

20. Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B-null mice

Author

Choi, Young Hun, Park, Sunhee, Hockman, Steven, Zmuda-Trzebiatowska, Emilia, Svennelid, Fredrik, Haluzik, Martin, Gavrilova, Oksana, Ahmad, Faiyaz, Pepin, Laurent, Napolitano, Maria, Taira, Masato, Sundler, Frank, Holst, Lena Stenson, Degerman, Eva, and Manganiello, Vincent C.

Subjects
Homeostasis -- Research, Mice -- Research, Phosphodiesterases -- Research, Medical research, Medicine, Experimental
Abstract

Cyclic nucleotide phosphodiesterase 3B (PDE3B) has been suggested to be critical for mediating insulin/IGF-1 inhibition of cAMP signaling in adipocytes, liver, and pancreatic [beta] cells. In Pde3b-KO adipocytes we found [...]

Published
2006

22. Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

Author

Ahlqvist, Emma, Osmark, Peter, Kuulasmaa, Tiina, Pilgaard, Kasper, Omar, Bilal, Brøns, Charlotte, Kotova, Olga, Zetterqvist, Anna V., Stančáková, Alena, Jonsson, Anna, Hansson, Ola, Kuusisto, Johanna, Kieffer, Timothy J., Tuomi, Tiinamaija, Isomaa, Bo, Madsbad, Sten, Gomez, Maria F., Poulsen, Pernille, Laakso, Markku, Degerman, Eva, Pihlajamäki, Jussi, Wierup, Nils, Vaag, Allan, Groop, Leif, and Lyssenko, Valeriya

Published
2013
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26. Airborne cell analysis

Author

Santesson, Sabina, Andersson, Martin, Degerman, Eva, Johansson, Thomas, Nilsson, Johan, and Nilsson, staffan

Subjects
Piezoelectric devices -- Design and construction, Air -- Microbiology, Fat cells -- Analysis, Imaging systems -- Usage, Lipolysis -- Analysis, Chemistry
Abstract

A miniaturized analysis system for the study of living cells and biochemical reactions in microdroplets was developed. The technique utilizes an in-house-developed piezoelectric flow-through droplet dispenser for precise reagent supply and an ultrasonic levitator for contactless sample handling. A few-cell study was performed with living primary adipocytes. Droplets (500 nL) containing 3-15 individual cells were acoustically levitated. The addition of (beta)-adrenergic agonists into the levitated droplet using the droplet dispenser stimulated adipocyte lipolysis, leading to free fatty acid release and a consequent pH decrease of the surrounding buffer. The addition of insulin antagonized lipolysis and hence also the decrease in pH. The changes in pH, i.e., the cell response in the droplet, were followed using a pH-dependent fluorophore continuously monitored by fluorescence imaging detection. An image analysis computer program was employed to calculate the droplet intensities. To counteract droplet evaporation, found to affect the fluorescence intensities, a separate dispenser was used to continually add water, thus keeping the droplet volume constant.

Published
2000

30. Insulin regulates Nedd4-2 via a PKB-dependent mechanism in HEI-OC1 auditory cells-crosstalks with sphingolipid and cAMP signaling.

Author

Pålbrink, Ann-Ki, Morén, Björn, Stenkula, Karin G., Magnusson, Måns, and Degerman, Eva

Subjects
DIABETES complications, INNER ear, WESTERN immunoblotting, MICROSCOPY, ANIMAL experimentation, PHOSPHOTRANSFERASES, WORTMANNIN, INSULIN, CELLULAR signal transduction, CELL communication, CERAMIDES, ENZYMES, TRANSFERASES, CELL lines, SPHINGOLIPIDS, PHOSPHORYLATION, ENZYME inhibitors, CARRIER proteins, METABOLITES, PHARMACODYNAMICS
Abstract

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2022
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34. Contributors

Author

Abrams, John M., primary, Adelman, John P., additional, Alcorn, Joseph L., additional, Alessi, Dario R., additional, Alexov, Emil, additional, Alford, Simon, additional, Alitalo, Kari, additional, Allison, James P., additional, Almo, Steven C., additional, Alory, Christelle, additional, Al-Shamkhani, Aymen, additional, Amundson, Sally A., additional, Anderson, Carl W., additional, Andersen, Jannik N., additional, Angel, Peter, additional, Appella, Ettore, additional, Arendshorst, William J., additional, Arkinstall, Steve, additional, Audhya, Anjon, additional, Avruch, Joseph, additional, Bader, Gary D., additional, Bagala, Cinzia, additional, Balch, William E., additional, Balsinde, Jesus, additional, Banerjee, Utpal, additional, Barford, David, additional, Bar-Sagi, Dafna, additional, Bartlett, Perry F., additional, Bastiaens, Philippe I.H., additional, Battelli, Chiara, additional, Baudhuin, Linnea M., additional, Beavil, Andrew J., additional, Beavil, Rebecca L., additional, Beavo, Joseph A., additional, Bello-Reuss, Elsa, additional, Bellum, Stephen, additional, Belmonte, Juan Carlos Izpisúa, additional, Bennett, Craig B., additional, Benovic, Jeffrey L., additional, Berridge, Michael J., additional, Beuning, Penny J., additional, Bhandari, Rashna, additional, Bhattacharya, Ananya, additional, Biel, Martin, additional, Bielinski, Vincent A., additional, Bilak, Hana, additional, Birnbaumer, Lutz, additional, Birrell, Geoff, additional, Bishop, Gail A., additional, Blackmer, Trillium, additional, Blackshear, Perry J., additional, Blattner, Christine, additional, Blaustein, Mordecai P., additional, Bokoch, Gary M., additional, Bonewald, Lynda F., additional, Bonomi, Marco, additional, Booden, Michelle A., additional, Boone, Charles, additional, Bootman, Martin D., additional, Bos, Johannes L., additional, Bradbury, Jane M., additional, Bradshaw, Ralph A., additional, Bresnick, Anne R., additional, Brevnova, Lena, additional, Brinkworth, Ross I., additional, Brown, Michael S., additional, Brown, Steven A., additional, Brunet, Anne, additional, Bucki, Robert, additional, Burgoyne, Robert D., additional, Buss, Janice E., additional, Butow, Ronald A., additional, Capdevila, Javier, additional, Carafoli, Ernesto, additional, Carlson, Cathrine R., additional, Carpenter, Graham, additional, Carrillo, Juan J., additional, Casey, Patrick J., additional, Catterall, William A., additional, Cerione, Richard A., additional, Cesareni, Gianni, additional, Chan, Andrew C., additional, Chang, Geoffrey, additional, Chao, Moses V., additional, Charbonneau, Harry, additional, Chen, Philip, additional, Cheng, Alan, additional, Chiu, Chris, additional, Chow, Dar-chone, additional, Chrisman, Ted D., additional, Christensen, Anne Elisabeth, additional, Chung, Jee Y., additional, Churchill, Grant C., additional, Ciechanover, Aaron, additional, Cingolani, Gino, additional, Claeysen, Sylvie, additional, Closset, Jean, additional, Cockcroft, Shamshad, additional, Cohen, Patricia T.W., additional, Cohen, Philip, additional, Colbran, Roger J., additional, Comstock, Clay E.S., additional, Conti, Marco, additional, Corbin, Jackie D., additional, Corda, Daniela, additional, Costagliola, Sabine, additional, Cote, Rick H., additional, Coughlin, Shaun R., additional, Cowart, L. Ashley, additional, Cox, Adrienne D., additional, Cragg, Mark S., additional, Crespo, José L., additional, Crosio, Claudia, additional, Daly, Christopher, additional, Damak, Sami, additional, Dasso, Mary, additional, David, Michael, additional, Davis, Anthony J., additional, Davis, Roger J., additional, Day, Richard N., additional, Degerman, Eva, additional, DeLano, Warren L., additional, Dell'Acqua, Mark L., additional, Délot, Emmanuèle, additional, Demple, Bruce, additional, Dennis, Edward A., additional, Denu, John M., additional, DePaoli-Roach, Anna A., additional, Der, Channing J., additional, de Rooij, Johan, additional, de Sauvage, Frederic, additional, Devreotes, Peter N., additional, Dewaste, Valérie, additional, Dickson, Robert B., additional, Diebold, Becky A., additional, Fiori, Pier Paolo Di, additional, Girolamo, Maria Di, additional, Diplexcito, Julie, additional, Dixon, Jack E., additional, Doms, Robert W., additional, Donoghue, Daniel J., additional, Doolittle, Russell F., additional, Døskeland, Stein Ove, additional, Dostmann, Wolfgang R.G., additional, Dreyer, Matthias K., additional, Du, Guo Guang, additional, Du, Keyong, additional, Duchen, Michael R., additional, Dunphy, William G., additional, Durgan, Joanne, additional, Dustin, Michael L., additional, Edwards, Peter A., additional, Egen, Jackson G., additional, Eiden, Lee E., additional, Elion, Elaine A., additional, Emr, Scott, additional, Engelhardt, Othmar G., additional, Erneux, Christophe, additional, Espenshade, Peter J., additional, Esplin, Edward D., additional, Evers, B. Mark, additional, Eyles, Joanne L., additional, Fame, Sheelagh, additional, Farquhar, Marilyn, additional, Feil, Robert, additional, Feng, Gui-Jie, additional, Fields, Stanley, additional, Fiordalisi, James J., additional, Firtel, Richard A., additional, Fitzgerald, Garret A., additional, Flint, Andrew, additional, Foiani, Marco, additional, Forman, Barry Marc, additional, Fornace, Albert J., additional, Francis, Sharron H., additional, Fritz, Günter, additional, Fruman, David A., additional, Galione, Antony, additional, Gandhi, Chris S., additional, Garbers, David L., additional, Garcia, K. Christopher, additional, Geiger, Benjamin, additional, Gerace, Larry, additional, Gerstner, Andrea, additional, Giaccia, Amato J., additional, Giannattasio, Michele, additional, Giguère, Vincent, additional, Glass, Christopher K., additional, Glennie, Martin J., additional, Glick, Jennifer L., additional, Goldstein, Joseph L., additional, Gopal, Venkatesh, additional, Gorospe, Myriam, additional, Govaerts, Cedric, additional, Graves, Paul R., additional, Gray, Patrick W., additional, Graziani, Irene, additional, Green, Douglas R., additional, Greenberg, Michael E., additional, Greenwald, Iva, additional, Gu, Haihua, additional, Gueven, Nuri, additional, Gutkind, J. Silvio, additional, Haeggström, Jesper Z., additional, Hall, Alan, additional, Hall, Michael N., additional, Haller, Otto, additional, Hamm, Heidi E., additional, Hannun, Yusef A., additional, Hansen, Carl A., additional, Harden, T. Kendall, additional, Hardie, D. Grahame, additional, Hasegawa, Kiminori, additional, Hawkins, Phillip T., additional, Haystead, Timothy A.J., additional, He, Xiao-lin, additional, Heizmann, Claus W., additional, Heldin, Carl-Henrik, additional, Hermiston, Michelle L., additional, Herrlich, Peter, additional, Hewat, Elizabeth A., additional, Hille, Bertil, additional, Hilton, Douglas J., additional, Hinchliffe, K.A., additional, Ho, Steffan N., additional, Ho, Su-Chin, additional, Hochstrasser, Mark, additional, Hofmann, Franz, additional, Hogue, Christopher W., additional, Hol, Wim G.J., additional, Holash, Jocelyn, additional, Holmgren, Robert A., additional, Honig, Barry, additional, Hostager, Bruce S., additional, Hubbard, Stevan R., additional, Huber, Michael, additional, Hunter, Tony, additional, Huttenlocher, Anna, additional, Hymowitz, Sarah G., additional, Ihle, James N., additional, Imler, Jean-Luc, additional, Irvine, R.F., additional, Isacoff, Ehud Y., additional, Iturrioz, Xavier, additional, Iversen, Lars F., additional, Iyengar, Ravi, additional, Jackson, Stephen P., additional, Jan, Lily Yeh, additional, Janiak-Spens, Fabiola, additional, Janmey, Paul A., additional, Jansen, Peter Gildsig, additional, Jarriault, Sophie, additional, Javitch, Jonathan A., additional, Jensen, Elwood V., additional, Jepsen, Kristen, additional, Jones, E. Yvonne, additional, Jones, Katherine A., additional, Jordan, J. Dedrick, additional, Joseph, Jomon, additional, Justement, Louis B., additional, Kafri, Yariv, additional, Kahn, Richard A., additional, Kang, Shin W., additional, Karlin, Arthur, additional, Kast-Woelbern, Heidi R., additional, Kaufman, Randal J., additional, Kazlauskas, Andrius, additional, Keen, James H., additional, Kemler, Rolf, additional, Kemp, Bruce E., additional, Kennedy, Mary B., additional, Kennedy, Matthew A., additional, Kikkawa, Ushio, additional, Kim, Albert H., additional, Kim, Soo-A, additional, Kim, Sung-Hou, additional, Kim, Youngjoo, additional, King-Jones, Kirst, additional, Kintner, Chris, additional, Kivimäe, Saul, additional, Klee, Claude B., additional, Klein, Rüdiger, additional, Kleppisch, Thomas, additional, Kliewer, Steven A., additional, Klinghoffer, Richard A., additional, Knoblich, Juergen A., additional, Kobe, Bostjan, additional, Kochs, George, additional, Kong-Beltran, Monica, additional, König, Rolf, additional, Koong, Albert C., additional, Korc, Murray, additional, Kornitzer, Daniel, additional, Kossiakoff, Anthony A., additional, Kotera, Jun, additional, Kovalenko, M.V., additional, Kozasa, Tohru, additional, Kozlov, Sergei, additional, Kozminski, Keith G., additional, Krugmann, Sonja, additional, Kuriyan, John, additional, Kurokawa, Riki, additional, Kwong, Peter D., additional, Lai, Wi S., additional, Lamar, Elise, additional, Lambert, Millard H., additional, Lambright, David G., additional, Lancet, Doron, additional, Landry, Reiko, additional, Langdon, Wallace Y., additional, Langeberg, Lorene K., additional, Lasko, Paul, additional, Latham, Vaughn, additional, Lavin, Martin F., additional, Lease, Kevin A., additional, Leffler, Hakon, additional, Lemmon, Mark A., additional, Leonard, Ann E., additional, Levitzki, Alexander, additional, Liao, Hong-Jun, additional, Liaw, Lucy, additional, Liberi, Giordano, additional, Lickert, Heiko, additional, Liddington, Robert C., additional, Lincoln, Thomas M., additional, Linder, Jürgen U., additional, Linder, Maurine E., additional, Liu, Hui, additional, Liu, Zhengchang, additional, Lohela, Marja K., additional, Louie, Sarah H., additional, Luttrell, Deirdre K., additional, Luttrell, Louis M., additional, Lyons, Karen M., additional, Macaulay, S. Lance, additional, Maceyka, Michael, additional, Maciag, Thomas, additional, Macian, Fernando, additional, MacKintosh, Carol, additional, MacLennan, David H., additional, Mahmood, Nadir A., additional, Malbon, Craig C., additional, Malik, Sohail, additional, Man, Orna, additional, Manahan, Carol L., additional, Mandinova, Anna, additional, Manganiello, Vincent C., additional, Manley, James L., additional, Mann, Matthias, additional, Manning, Gerald, additional, Manser, Ed, additional, Margeta-Mitrovic, Marta, additional, Margolskee, Robert F., additional, Marinissen, Julia, additional, Mariuzza, Roy A., additional, Marmor, Mina D., additional, Martin, G. Steven, additional, Martin, Karen H., additional, Martinez, Sergio E., additional, Mathews, Michael B., additional, Mayer, Bruce J., additional, Mayer, Mark L., additional, Mazzoni, Maria R., additional, McCormick, Frank, additional, McGowan, Clare H., additional, McKay, Melissa M., additional, McKeehan, Wallace L., additional, McLean, Alison J., additional, Means, Anthony R., additional, Meili, Ruedi, additional, Meng, Jingwei, additional, Merchant, Mark, additional, Mercurio, Frank, additional, Milligan, Graeme, additional, Ming, Guo-Li, additional, Minor, Daniel L., additional, Moghal, Nadeem, additional, Møller, Neils Peter H., additional, Mongillo, Marco, additional, Montminy, Marc, additional, Moon, Randall T., additional, Morimoto, Richard I., additional, Moss, Stephen E., additional, Mott, Helen R., additional, Mouta, Carla, additional, Muda, Marco, additional, Mumby, Marc C., additional, Murphy, Gretchen A., additional, Muzi-Falconi, Marco, additional, Nagaraj, Raghavendra, additional, Nahorski, Stefan R., additional, Nairn, Angus C., additional, Nash, Piers, additional, Neel, Benjamin G., additional, Newton, Alexandra C., additional, Nishizuka, Yasutomi, additional, Noel, Joseph P., additional, Nollen, Ellen A.A., additional, Nooren, Irene M.A., additional, O'Connor, Rodney, additional, Offermanns, Stefan, additional, Olender, Tsviya, additional, Ong, Shao-En, additional, Owen, Darerca, additional, Pagliari, Lisa J., additional, Pao, Lily, additional, Papaconstantinou, John, additional, Pardo, Leonardo, additional, Park, Hay-Oak, additional, Park, Young Chul, additional, Parker, Peter J., additional, Parsons, J. Thomas, additional, Passner, J.M., additional, Pawson, Tony, additional, Pelliccioli, Achille, additional, Perez-Polo, J. Regino, additional, Perrimon, Norbert, additional, Petite, Fabrice G., additional, Petroulakis, Emmanuel, additional, Pfaff, Samuel L., additional, Piehler, Jacob, additional, Pike, Linda J., additional, Pinkoski, Michael J., additional, Pixley, Fiona J., additional, Plevani, Paolo, additional, Poo, Mu-ming, additional, Pozzan, Tullioi, additional, Prescott, Stephen M., additional, Prudovsky, Igor, additional, Putney, James W., additional, Radimerski, Thomas, additional, Radzio-Andzelm, Elzbieta, additional, Ram, Prahlad T., additional, Rameh, Lucia, additional, Ramljak, Danica, additional, Ranscht, Barbara, additional, Rao, Anjana, additional, Raport, Carol J., additional, Reeves, Jacqueline D., additional, Rehman, Holger, additional, Reichman, Trevor W., additional, Reiter, Eric, additional, Resnick, Michael A., additional, Reth, Michael, additional, Rhee, Sue Goo, additional, Richter, Joel D., additional, Rietze, Rodney L., additional, Rini, James M., additional, Ripperger, Jürgen A., additional, Rizo, Josep, additional, Robishaw, Janet D., additional, Roderick, H. Llewelyn, additional, Roeder, Robert G., additional, Rohrschneider, Larry R., additional, Ron, David, additional, Rosenfeld, Michael G., additional, Rosenfeldt, Hans, additional, Rossman, Kent L., additional, Roth, Christopher B., additional, Rudolph, Markus G., additional, Ruppelt, Anja, additional, Saez, Lino, additional, Sakmar, Thomas P., additional, Salvesen, Guy S., additional, Sassone-Corsi, Paolo, additional, Saxe, Charles L., additional, Schäfer, Beat W., additional, Schibler, Ueli, additional, Schindler, Christian W., additional, Schmelzle, Tobias, additional, Schmid, Sandra L., additional, Schmidt, Anja, additional, Schmidt, Eric F., additional, Schreiber, Gideon, additional, Schultz, Joachim E., additional, Schwaller, Beat, additional, Schwamborn, Klaus, additional, Schwartz, Thue, additional, Schwindinger, William F., additional, Scita, Giorgio, additional, Scott, John D., additional, Scott, Shaun, additional, Seebeck, Thomas, additional, Serhan, Charles N., additional, Shabb, John B., additional, Shaw, Andrey S., additional, Shears, Stephen B., additional, Shenolikar, Shirish, additional, Shi, Lei, additional, Shin, Chanseok, additional, Shiozaki, Kazuhiro, additional, Shokat, Kevan M., additional, Shuttleworth, Trevor J., additional, Siderovski, David P., additional, Siegelbaum, Steven A., additional, Silverstein, Adam M., additional, Singer, Robert H., additional, Skinner, Michael K., additional, Slack-Davis, Jill K., additional, Smerdon, Stephen J., additional, Smith, Graeme C.M., additional, Smits, Guillaume, additional, Smolik, Sarah M., additional, Smotrys, Jessica E., additional, Smyth, Emer M., additional, Snyder, Jason T., additional, Sogame, Naoko, additional, Soldi, Raffaella, additional, Sondek, John, additional, Sonenberg, Nahum, additional, Sonneberg, Erica Dutil, additional, Sparrow, Lindsay G., additional, Spiegel, Sarah, additional, Sprang, Stephen R., additional, Srivastava, Deepak, additional, Stanfield, Robyn L., additional, Stanley, E. Richard, additional, Stauber, Deborah J., additional, Stefan, Christopher, additional, Stenson-Holst, Lena, additional, Stephens, Len, additional, Sternberg, Paul W., additional, Sternweis, Paul C., additional, Steward, Ruth, additional, Stickney, John T., additional, Stoker, Andrew W., additional, Strittmatter, Stephen M., additional, Stronach, Beth E., additional, Strong, Roland K., additional, Stroud, Robert M., additional, Südhof, Thomas C., additional, Sunahara, Roger K., additional, Sutton, Brian J., additional, Szabolcs, Sipeki, additional, Tang, Xiao-Bo, additional, Taskén, Kjetil, additional, Tatebe, Hisashi, additional, Tauszig-Delamasure, Servane, additional, Taylor, Colin W., additional, Taylor, Garry L., additional, Taylor, Laura J., additional, Taylor, Susan S., additional, Thomas, George, additional, Thomas, Robert P., additional, Thompson, E. Brad, additional, Thompson, Michael J., additional, Thornton, Janet M., additional, Thummel, Carl S., additional, Togashi, Hideaki, additional, Tong, Amy Hin Yan, additional, Tonks, Nicholas K., additional, Tontonoz, Peter, additional, Topham, M.K., additional, Torgersen, Knut Martin, additional, Tran, Hien, additional, Tremblay, Michel L., additional, Tsai, Ming-Jer, additional, Tsai, Sophia Y., additional, Tsunoda, Susan, additional, Turley, Stewart, additional, Tyson, Darren, additional, Van Etten, Robert L., additional, Vassart, Gilbert, additional, Verveer, Peter J., additional, Vlaeminck, Virginie, additional, de Vos, Abraham M., additional, Voss, Ty C., additional, Walczak, Robert, additional, Walker, Graham C., additional, Walker, John C., additional, Walter, Gernot, additional, Walter, Mark R., additional, Wang, Fen, additional, Wang, Jean Y.J., additional, Wang, Weiru, additional, Ward, Richard J., additional, Wedegaertner, Philip, additional, Wehrle, Christian, additional, Weiss, Arthur, additional, Weiss, Jamie L., additional, Wells, Alan, additional, Werner, Claudia, additional, West, Ann H., additional, Weston, Marie C., additional, Westwick, John K., additional, Wetterholm, Anders, additional, White, Morris F., additional, Whitman, Malcolm, additional, Whorton, Matt R., additional, Wiesmann, Christian, additional, Williams, Roger L., additional, Willis, William D., additional, Willson, Timothy M., additional, Wilson, Ian A., additional, Wiser, Ofer, additional, Wishart, Matthew J., additional, Wittinghofer, Alfred, additional, Woodgett, James R., additional, Worthylake, David K., additional, Wrana, Jeffrey L., additional, Wu, Hao, additional, Xiao, Yijin, additional, Xu, H. Eric, additional, Xu, Yan, additional, Xu, Zheng, additional, Yaffe, Michael B., additional, Yamada, Kenneth M., additional, Yang, Seun-Ah, additional, Yang, Wannian, additional, Yarden, Yosef, additional, Ye, Hong, additional, Ye, Weilan, additional, Yeates, Todd O., additional, Yin, Helen L., additional, York, John D., additional, Young, Edgar C., additional, Young, Kenneth W., additional, Young, Matthew A., additional, Young, Michael W., additional, Yu, Minmin, additional, Zaccai, Nathan R., additional, Zaccolo, Manuela, additional, Zamir, Eli, additional, von Zastrow, Mark, additional, Zhang, Chao, additional, Zhang, Xuewu, additional, Zhang, Zhong-Yin, additional, Zhou, Wenhong, additional, and Zoraghi, Roya, additional

Published
2003
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37. Characterization of two recombinant PDE3 (cGMP-inhibited cyclic nucleotide phosphodiesterase) isoforms, RcGIP1 and HcGIP2, expressed in NIH 3006 murine fibroblasts and Sf6 insect cells

Author

Leroy, Marie-Josephe, Degerman, Eva, Taira, Masato, Murata, Taku, Wang, Lu Hua, Movsesian, Matthew A., Meacci, Elisabetta, and Manganiello, Vincent C.

Subjects
Phosphodiesterases -- Research, Amino acid sequence -- Observations, Biological sciences, Chemistry
Abstract

The immunologic properties of the recombinant rat cGMP-inhibited cyclic nucleotide phosphodiesterase (RcGIP1) and human GIP2 (HcGIP2), expressed in NIH 3006 murine fibroblasts and Sf6 insect cells, are similar to that of the native enzymes. The recombinant enzymes have a high cAMP affinity, and are sensitive to cGI PDE inhibitors and cGMP. The N-terminal is necessary for membrane binding of the enzymes. The amino acid sequence of RcGIP1 and HcGIP2 is highly similar in the catalytic regions but dissimilar in the N-terminal regulatory regions.

Published
1996

43. Branched short-chain fatty acids modulate glucose and lipid metabolism in primary adipocytes

Author

Heimann, Emilia, Nyman, Margareta, Pålbrink, Ann-Ki, Lindkvist-Petersson, Karin, and Degerman, Eva

Subjects
obesity, branched short-chain fatty acids, short-chain fatty acids, type 2 diabetes, adipocyte, metabolism, Research Paper
Abstract

Short-chain fatty acids (SCFAs), e.g. acetic acid, propionic acid and butyric acid, generated through colonic fermentation of dietary fibers, have been shown to reach the systemic circulation at micromolar concentrations. Moreover, SCFAs have been conferred anti-obesity properties in both animal models and human subjects. Branched SCFAs (BSCFAs), e.g., isobutyric and isovaleric acid, are generated by fermentation of branched amino acids, generated from undigested protein reaching colon. However, BSCFAs have been sparsely investigated when referring to effects on energy metabolism. Here we primarily investigate the effects of isobutyric acid and isovaleric acid on glucose and lipid metabolism in primary rat and human adipocytes. BSCFAs inhibited both cAMP-mediated lipolysis and insulin-stimulated de novo lipogenesis at 10 mM, whereas isobutyric acid potentiated insulin-stimulated glucose uptake by all concentrations (1, 3 and 10 mM) in rat adipocytes. For human adipocytes, only SCFAs inhibited lipolysis at 10 mM. In both in vitro models, BSCFAs and SCFAs reduced phosphorylation of hormone sensitive lipase, a rate limiting enzyme in lipolysis. In addition, BSCFAs and SCFAs, in contrast to insulin, inhibited lipolysis in the presence of wortmannin, a phosphatidylinositide 3-kinase inhibitor and OPC3911, a phosphodiesterase 3 inhibitor in rat adipocytes. Furthermore, BSCFAs and SCFAs reduced insulin-mediated phosphorylation of protein kinase B. To conclude, BSCFAs have effects on adipocyte lipid and glucose metabolism that can contribute to improved insulin sensitivity in individuals with disturbed metabolism.

Published
2016

44. ceramide influences the expression and insulin-mediated regulation of cyclic nucleotide phosphodiesterase 3B and lipolysis in 3T3-L1 adipocytes

Author

Mei, Jie, Holst, Lena Stenson, Landstrom, Tova Rahn, Holm, Cecilia, Brindley, David, Manganiello, Vincent, and Degerman, Eva

Subjects
Biological transport -- Research -- Physiological aspects, Diabetes -- Research, Insulin -- Research, Fatty acid metabolism -- Physiological aspects -- Research, Health, Physiological aspects, Research
Abstract

Cyclic nucleotide phosphodiesterase (PDE) 3B plays an important role in the antilipolytic action of insulin and, thereby, the release of fatty acids from adipocytes. Increased concentrations of circulating fatty acids [...]

Published
2002

47. Contributors

Author

Alvarez, Robert, primary, Baecker, Preston A., additional, Belfrage, Per, additional, Christensen, Siegfried B., additional, Conti, Marco, additional, Corbin, Jackie D., additional, Daniels, Donald V., additional, Degerman, Eva, additional, Dent, Gordon, additional, Devens, Bruce, additional, De Wolf, Walter E., additional, Eglen, Richard M., additional, Engelstätter, Renate, additional, Ferguson, Ken, additional, Fischmeister, Rodolphe, additional, Fong, T. Annie T., additional, Francis, Sharron H., additional, Giembycz, Mark A., additional, Grondin, Pascal, additional, Hatzelmann, Armin, additional, Hickie, Robert A., additional, Kedev, Sasko, additional, Komas, Narcisse, additional, Loughney, Kate, additional, Manganiello, Vincent C., additional, Mazzoni, Lazzarro, additional, Méry, Pierre-François, additional, Morley, John, additional, Movsesian, Matthew, additional, Pavoine, Catherine, additional, Pecker, Françoise, additional, Rabe, Klaus F., additional, Ryan, M. Dominic, additional, Schudt, Christian, additional, Sekhar, Konjeti R., additional, Sharma, Rajendra K., additional, Shelton, Earl R., additional, Silver, Paul J., additional, Souness, John E., additional, Tenor, Hermann, additional, Torphy, Theodore J., additional, and Wilhelm, Robert, additional

Published
1996
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