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Kelly D McCall
Kelly D McCall
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Dawn Holliday
Dawn Holliday
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Eric Dickerson
Eric Dickerson
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Brian Wallace
Brian Wallace
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Anthony L Schwartz
Anthony L Schwartz
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Christopher Schwartz
Christopher Schwartz
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Christopher J Lewis
Christopher J Lewis
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Leonard D Kohn
Leonard D Kohn
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Frank L Schwartz
Frank L Schwartz
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
Department of Specialty Medicine, Appalachian Rural Health Institute, Edison Biotechnology Institute, Department of Biomedical Sciences, Biomedical Engineering Program, Interthyr Corporation, Diabetes Research Center
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Visceral adipocytes and associated macrophages produce and release excessive amounts of biologically active inflammatory cytokines via the portal and systemic vascular system, which induce insulin resistance in insulin target tissues such as fat, liver, and muscle. Free fatty acids (FFAs) absorbed via the portal system or released from adipocytes also induce insulin resistance. In this report, we show that phenylmethimazole (C10) blocks basal IL6 and leptin production as well as basal Socs-3 expression in fully differentiated 3T3L1 cells (3T3L1 adipocytes) without affecting insulin-stimulated AKT signaling. In addition, C10 inhibits palmitate-induced IL6 and iNos up-regulation in both 3T3L1 adipocytes and RAW 264.7 macrophages, LPS-induced NF-κB and IFN-β activation in 3T3L1 cells, and LPS-induced iNos, Ifn- β, Il1 β, Cxcl10, and Il6 expression in RAW 264.7 macrophages. C10 also blocks palmitate-induced Socs-3 up-regulation and insulin receptor substrate-1 (IRS-1) serine 307 phosphorylation in 3T3L1 adipocytes. Additionally, we show for the first time that although palmitate increases IRS-1 serine 307 phosphorylation in 3T3L1 adipocytes, AKT serine 473 phosphorylation is enhanced, not reduced, by palmitate. These results suggest that through inhibition of FFA-mediated signaling in adipocytes and associated macrophages, as well as possibly other insulin target cells/tissues (i.e. non-immune cells), C10 might be efficacious to prevent or reverse cytokine-induced insulin resistance seen in obesity-related insulin resistance and type 2 diabetes mellitus.
Berit Svendsen
Berit Svendsen
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Ramona Pais
Ramona Pais
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Maja S Engelstoft
Maja S Engelstoft
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Nikolay B Milev
Nikolay B Milev
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Paul Richards
Paul Richards
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Charlotte B Christiansen
Charlotte B Christiansen
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Kristoffer L Egerod
Kristoffer L Egerod
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Signe M Jensen
Signe M Jensen
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Abdella M Habib
Abdella M Habib
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Fiona M Gribble
Fiona M Gribble
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Thue W Schwartz
Thue W Schwartz
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Frank Reimann
Frank Reimann
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Jens J Holst
Jens J Holst
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, Wellcome Trust – MRC Institute of Metabolic Science, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark
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The incretin hormones glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from intestinal endocrine cells, the so-called L- and K-cells. The cells are derived from a common precursor and are highly related, and co-expression of the two hormones in so-called L/K-cells has been reported. To investigate the relationship between the GLP1- and GIP-producing cells more closely, we generated a transgenic mouse model expressing a fluorescent marker in GIP-positive cells. In combination with a mouse strain with fluorescent GLP1 cells, we were able to estimate the overlap between the two cell types. Furthermore, we used primary cultured intestinal cells and isolated perfused mouse intestine to measure the secretion of GIP and GLP1 in response to different stimuli. Overlapping GLP1 and GIP cells were rare (∼5%). KCl, glucose and forskolin+IBMX increased the secretion of both GLP1 and GIP, whereas bombesin/neuromedin C only stimulated GLP1 secretion. Expression analysis showed high expression of the bombesin 2 receptor in GLP1 positive cells, but no expression in GIP-positive cells. These data indicate both expressional and functional differences between the GLP1-producing ‘L-cell’ and the GIP-producing ‘K-cell’.
