title: Contraction stimulates muscle glucose uptake independent of atypical PKC.
abstract: Exercise increases skeletal muscle glucose uptake, but the underlying mechanisms are only partially understood. The atypical protein kinase C (PKC) isoforms λ and ζ (PKC-λ/ζ) have been shown to be necessary for insulin-, AICAR-, and metformin-stimulated glucose uptake in skeletal muscle, but not for treadmill exercise-stimulated muscle glucose uptake. To investigate if PKC-λ/ζ activity is required for contraction-stimulated muscle glucose uptake, we used mice with tibialis anterior muscle-specific overexpression of an empty vector (WT), wild-type PKC-ζ (PKC-ζ(WT)), or an enzymatically inactive T410A-PKC-ζ mutant (PKC-ζ(T410A)). We also studied skeletal muscle-specific PKC-λ knockout (MλKO) mice. Basal glucose uptake was similar between WT, PKC-ζ(WT), and PKC-ζ(T410A) tibialis anterior muscles. In contrast, in situ contraction-stimulated glucose uptake was increased in PKC-ζ(T410A) tibialis anterior muscles compared to WT or PKC-ζ(WT) tibialis anterior muscles. Furthermore, in vitro contraction-stimulated glucose uptake was greater in soleus muscles of MλKO mice than WT controls. Thus, loss of PKC-λ/ζ activity increases contraction-stimulated muscle glucose uptake. These data clearly demonstrate that PKC-λζ activity is not necessary for contraction-stimulated glucose uptake.
authors.affiliation: Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yu
authors.affiliation: Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Nobuharu L
authors.initials: NL
authors.lastname: Fujii
authors.affiliation: Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Taro
authors.initials: T
authors.lastname: Toyoda
authors.affiliation: Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Ding
authors.initials: D
authors.lastname: An
authors.affiliation: James A. Haley Veterans Medical Center, Tampa, Florida.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Farese
authors.affiliation: The Biotechnology Center of Oslo, University of Oslo, Blindern, Oslo, Norway.
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.affiliation: Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hirshman
authors.affiliation: Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Joram D
authors.initials: JD
authors.lastname: Mul
authors.affiliation: Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts Laurie.Goodyear@joslin.harvard.edu.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
keywords: Contraction‐stimulated glucose uptake; Glucose uptake; Muscle contraction; atypical PKC