title: Tissue-specific differences in the development of insulin resistance in a mouse model for type 1 diabetes.
abstract: Although insulin resistance is known to underlie type 2 diabetes, its role in the development of type 1 diabetes has been gaining increasing interest. In a model of type 1 diabetes, the nonobese diabetic (NOD) mouse, we found that insulin resistance driven by lipid- and glucose-independent mechanisms is already present in the liver of prediabetic mice. Hepatic insulin resistance is associated with a transient rise in mitochondrial respiration followed by increased production of lipid peroxides and c-Jun N-terminal kinase activity. At the onset of diabetes, increased adipose tissue lipolysis promotes myocellular diacylglycerol accumulation. This is paralleled by increased myocellular protein kinase C θ activity and serum fetuin A levels. Muscle mitochondrial oxidative capacity is unchanged at the onset but decreases at later stages of diabetes. In conclusion, hepatic and muscle insulin resistance manifest at different stages and involve distinct cellular mechanisms during the development of diabetes in the NOD mouse.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Jelenik
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Gilles
authors.initials: G
authors.lastname: Séquaris
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Kirti
authors.initials: K
authors.lastname: Kaul
authors.affiliation: German Center for Diabetes Research, Partner Düsseldorf, Germany Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Phielix
authors.affiliation: German Center for Diabetes Research, Partner Düsseldorf, Germany Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kotzka
authors.affiliation: German Center for Diabetes Research, Partner Düsseldorf, Germany Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Knebel
authors.affiliation: German Center for Diabetes Research, Partner Düsseldorf, Germany Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weiß
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Reinbeck
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Janke
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nowotny
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Partke
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT.
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany Department of Endocrinology and Diabetology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany German Center for Diabetes Research, Partner Düsseldorf, Germany Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany Department of Endocrinology and Diabetology, Heinrich-Heine University, Düsseldorf, Germany michael.roden@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D007333:Insulin Resistance / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D011236:Prediabetic State / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism
chemical_list: D008054:Lipid Peroxides; D060749:alpha-2-HS-Glycoprotein; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases