Contraction stimulates muscle glucose uptake independent of atypical PKC.

Haiyan Yu,Ding An,Michael F Hirshman,Michael Leitges,Taro Toyoda,Robert V Farese,Nobuharu L Fujii,Joram D Mul,Laurie J Goodyear

doi:10.14814/phy2.12565

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, insitu contraction-stimulated glucose uptake was increased in PKC-ζ(T410A) tibialis anterior muscles compared to WT or PKC-ζ(WT) tibialis anterior muscles. Furthermore, invitro 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.

Highlights

Normal regulation of glucose transport into skeletal muscle in response to physical exercise or postprandial insulin stimulation is critical for the maintenance of whole-body glucose homeostasis (Richter and Hargreaves 2013; Schwartz et al 2013)
The goal of this study was to determine if Atypical protein kinase C (aPKC) activity is necessary for contraction-stimulated glucose uptake in skeletal muscle
We found that aPKC activity is not required for contraction-induced glucose uptake, and impairment of aPKC activity resulted in significant improvements in contraction-induced muscle glucose uptake

Summary

Introduction

Normal regulation of glucose transport into skeletal muscle in response to physical exercise or postprandial insulin stimulation is critical for the maintenance of whole-body glucose homeostasis (Richter and Hargreaves 2013; Schwartz et al 2013). Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society While exercise and muscle contractile activity cause GLUT4 translocation, it is well established that the initiating signaling molecules that mediate this process are distinct from that of insulin (Ploug et al 1987; Constable et al 1988; Douen et al 1990; Hayashi et al 1998; Lemieux et al 2000). The signaling proteins that regulate exercise- and contraction-stimulated glucose uptake are still not clearly understood, and there is considerable evidence that redundant signaling mechanisms may control this important physiological process (Rockl et al 2008)

Objectives

Methods

Results

Conclusion