Short-term Caloric Restriction Does Not Modify the In Vivo Insulin Signaling Pathway Leading to Akt Activation in Skeletal Muscle of Ames Dwarf (Prop1df/Prop1df) Mice

D. P. Argentino; M. C. Muñoz; J. S. Rocha; A. Bartke; D. Turyn; F. P. Dominici

doi:10.1055/s-2005-870577

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2005; 37(11): 672-679
DOI: 10.1055/s-2005-870577

Original Basic

Short-term Caloric Restriction Does Not Modify the In Vivo Insulin Signaling Pathway Leading to Akt Activation in Skeletal Muscle of Ames Dwarf (Prop1^df/Prop1^df) Mice

D. P. Argentino¹ , M. C. Muñoz¹ , J. S. Rocha^2, ³ , A. Bartke² , D. Turyn¹ , F. P. Dominici¹

¹Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina
²Department of Physiology and Medicine, School of Medicine, Southern Illinois University, IL, USA
³Laboratory of Cellular Biology, Department of Morphology, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Brazil

Abstract

The purpose of this study was to analyze the interaction between caloric restriction (CR) and the dwarf mutation at the level of insulin sensitivity and signal transduction. To this end, we analyzed the in vivo status of the insulin signaling system in skeletal muscle from Ames dwarf (df/df) and normal mice fed ad libitum or subjected to short-term (20-day) CR. We measured insulin-stimulated phosphorylation of the IR and IRS-1, IRS-1-p85 association and Akt activation, and the abundance of the IR, IRS-1, p85, GLUT-4 and IGF-1 receptor in skeletal muscle. In terms of glucose homeostasis, the response to CR was different in both groups of animals. In normal animals, CR induced a significant reduction in both circulating insulin and glucose levels, while CR did not modify these parameters in df/df mice. We did not find any significant alteration in either activation or abundance of signaling molecules analyzed after short-term CR in either normal or Ames dwarf mice. We conclude that the initial adaptation to CR in normal mice is an increase in insulin sensitivity without changes in insulin signal transduction, and that this adaptation is not evidenced in df/df mice, probably since they are already hypersensitive to insulin.

Key words

Aging - caloric restriction - growth hormone - IGF-1 - insulin receptor - IRS-1 - insulin sensitivity

Full Text

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