PMID- 15664729 OWN - NLM STAT- MEDLINE DCOM- 20050525 LR - 20131121 IS - 0531-5565 (Print) IS - 0531-5565 (Linking) VI - 40 IP - 1-2 DP - 2005 Jan-Feb TI - Effects of long-term caloric restriction on glucose homeostasis and on the first steps of the insulin signaling system in skeletal muscle of normal and Ames dwarf (Prop1df/Prop1df) mice. PG - 27-35 AB - Ames dwarf mice are a model of retarded aging and extended longevity and display enhanced insulin sensitivity. Caloric restriction (CR) and the dwarf mutation have additive effects on lifespan. To begin to understand the mechanisms behind this effect, an analysis of the in vivo status of the insulin signaling system was performed in skeletal muscle from Ames dwarf (df/df) and normal mice fed ad libitum or subjected to long-term (over 1 year) CR. 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, together with an increase in the in vivo insulin-stimulated phosphorylation of the IR, a trend towards an increase in the in vivo insulin-stimulated phosphorylation levels of IR substrate-1, and an increase in the abundance of GLUT4 in muscle. In contrast, CR did not modify none of these parameters in df/df mice. Interestingly, CR induced a reduction in the p85 subunit of phosphatidylinositol 3-kinase abundance in skeletal muscle in both groups of animals. These results suggest that in skeletal muscle, long-term CR induces different effects on the first steps of the insulin signaling system in normal mice than in df/df mice. FAU - Argentino, Danila Paula AU - Argentino DP AD - Facultad de Farmacia y Bioquimica, Instituto de Quimica y Fisicoquimica Biologicas (UBA-CONICET), Junin 956, 1113AAD Buenos Aires, Argentina. FAU - Dominici, Fernando Pablo AU - Dominici FP FAU - Munoz, Marina Cecilia AU - Munoz MC FAU - Al-Regaiey, Khalid AU - Al-Regaiey K FAU - Bartke, Andrzej AU - Bartke A FAU - Turyn, Daniel AU - Turyn D LA - eng GR - AG 19899/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Exp Gerontol JT - Experimental gerontology JID - 0047061 RN - 0 (Blood Glucose) RN - 0 (Glucose Transporter Type 4) RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs1 protein, mouse) RN - 0 (Monosaccharide Transport Proteins) RN - 0 (Muscle Proteins) RN - 0 (Phosphoproteins) RN - 0 (Slc2a4 protein, mouse) RN - 42HK56048U (Tyrosine) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) SB - IM MH - Aging/metabolism MH - Animals MH - Blood Glucose/*metabolism MH - Body Weight/physiology MH - *Caloric Restriction MH - Dwarfism/metabolism MH - Female MH - Glucose Transporter Type 4 MH - Insulin/blood/*physiology MH - Insulin Receptor Substrate Proteins MH - Longevity/physiology MH - Mice MH - Mice, Mutant Strains MH - Monosaccharide Transport Proteins/metabolism MH - Muscle Proteins/metabolism MH - Muscle, Skeletal/*metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoproteins/metabolism MH - Phosphorylation MH - Signal Transduction/physiology MH - Tyrosine/metabolism EDAT- 2005/01/25 09:00 MHDA- 2005/05/26 09:00 CRDT- 2005/01/25 09:00 PHST- 2004/07/15 00:00 [received] PHST- 2004/08/31 00:00 [revised] PHST- 2004/09/13 00:00 [accepted] PHST- 2005/01/25 09:00 [pubmed] PHST- 2005/05/26 09:00 [medline] PHST- 2005/01/25 09:00 [entrez] AID - S0531-5565(04)00297-9 [pii] AID - 10.1016/j.exger.2004.09.005 [doi] PST - ppublish SO - Exp Gerontol. 2005 Jan-Feb;40(1-2):27-35. doi: 10.1016/j.exger.2004.09.005.