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Short‐term Caloric Restriction Improves Glucose Tolerance in Older Mice Independent of Changes in SIRT‐1
Author(s) -
Rippe Catarina,
Lesniewski Lisa A,
Donato Anthony J,
Seals Douglas R
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.990.33
Subject(s) - medicine , endocrinology , insulin , skeletal muscle , glucose homeostasis , sirtuin , white adipose tissue , adipose tissue , glucose uptake , chemistry , caloric theory , insulin resistance , nad+ kinase , biochemistry , enzyme
In rodents, life‐long caloric restriction (CR) preserves in vivo glucose‐insulin function with aging, possibly by increasing the protein deacetylase sirtuin 1 (SIRT‐1). Because life‐long CR is not feasible in humans, we determined if short‐term CR could improve glucose‐insulin function in old mice and the role of SIRT‐1. Old (30 mo) male B6D2F1‐mice were fed either ad libitum (AL, n=4‐6) or were restricted to 70% of AL for 5 weeks after 2 weeks of progressive restriction (CR, n=4‐6). At baseline, no differences were observed in the area under the curve (AUC) for glucose or insulin during an i.p glucose tolerance test between AL and CR. The AUC for glucose was not significantly different after vs. before CR (10,085±211 vs. 11,844±1371 mg/dl*min, P=0.1) or AL (12,720±1343 vs. 12,486±1085, P=0.9). However, the AUC for insulin was 77% lower after CR (34±8 vs. 149±22 ng/ml*min, P<0.05), but was 77% greater after AL (234±34 vs. 132±12, P<0.05). CR did not affect SIRT‐1 protein expression in either skeletal muscle or white adipose tissue (WAT) (P=0.9 and P=0.8, post CR vs. AL), but increased expression of insulin receptor substrate‐1 (IRS‐1) by 190% in muscle (2.8±0.6 vs. 1.0±0.2, P<0.05) and by 150% in WAT (2.5±1.0 vs. 1.0±0.4, P<0.005). Our findings indicate that short‐term CR markedly improves insulin sensitivity in old mice independent of changes in peripheral SIRT‐1 expression. The CR‐induced improvement in insulin sensitivity is associated with robust increases in IRS‐1 expression in both skeletal muscle and WAT. NIH AG006537 , AG015897 , AG029337 , AG000279 , The Swedish Medical Research Council