title: JNK1 deficiency does not enhance muscle glucose metabolism in lean mice.
abstract: Mice deficient in c-jun-NH(2)-terminal kinase 1 (JNK1) exhibit decreased fasting blood glucose and insulin levels, and protection against obesity-induced insulin resistance, suggesting increased glucose disposal into skeletal muscle. Thus, we assessed whether JNK1 deficiency enhances muscle glucose metabolism. Ex vivo insulin or contraction-induced muscle [(3)H]2-deoxyglucose uptake was not altered in JNK1 knockout mice, demonstrating that JNK1 does not regulate blood glucose levels via direct alterations in muscle. In vivo muscle [(3)H]2-deoxyglucose uptake in response to a glucose injection was also not enhanced by JNK1 deficiency, demonstrating that a circulating factor was not required to observe altered muscle glucose uptake in the knockout mice. JNK1 deficiency did not affect muscle glycogen levels or the protein expression of key molecules involved in glucose metabolism. This study is the first to directly demonstrate that enhanced skeletal muscle glucose metabolism does not underlie the beneficial effects of JNK1 deficiency in lean mice.
authors.affiliation: Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Witczak
authors.forename: M F
authors.initials: MF
authors.lastname: Hirshman
authors.forename: N
authors.initials: N
authors.lastname: Jessen
authors.forename: N
authors.initials: N
authors.lastname: Fujii
authors.forename: M M
authors.initials: MM
authors.lastname: Seifert
authors.forename: J
authors.initials: J
authors.lastname: Brandauer
authors.forename: G S
authors.initials: GS
authors.lastname: Hotamisligil
authors.forename: L J
authors.initials: LJ
authors.lastname: Goodyear
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D013851:Thinness / Q000378:metabolism*
chemical_list: D048055:Mitogen-Activated Protein Kinase 8