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Aging increases susceptibility to western diet‐induced glucose intolerance and insulin resistance in mice
Author(s) -
Russell Molly J,
Folian Brian J,
Durrant Jessica R,
Connell Melanie L,
Seals Douglas R,
Lesniewski Lisa A
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.990.18
Subject(s) - medicine , endocrinology , insulin resistance , insulin , chemistry , adipose tissue , area under the curve , glucose clamp technique , pancreatic hormone
Aging may increase vulnerability for developing glucose‐insulin dysfunction with consumption of a high fat or "western" diet (WD). Young (Y, 6‐8 mo, N=4‐8/group) and old (O, 29‐31 mo, N=4‐8/group) B6D2F1 mice were fed normal chow (NC, 14% fat by kcal) or WD (40% fat) for 8 weeks. On NC during glucose tolerance tests the areas under the curves for glucose (AUC g ) and insulin (AUC i ) were not different (15815±665 vs. 14611±1261 mg/dl*min, Y vs. O, P=0.2) and greater (38.1±4.4 vs. 28.1±1.1 ng/ml*min, P<0.05), respectively, in O mice, but there were no age‐group differences (P=0.49) in glucose infusion rates (GIR) during hyperinsulinemic‐euglycemic clamps (6 mU/kg/min). WD increased AUC g in both Y and O (to 18175±653 and 19947±1889 mg/dl*min, respectively, both P=0.01), but increased the insulin response to a glucose challenge only in O mice (AUC i : 79.1±7.3 ng/ml*min, P<0.01 vs. ONC). Compared with NC, WD markedly reduced GIR in O mice (30±6 vs. 51±5 mg/kg/min, P< 0.05), but only tended to do so in Y mice (37±3 vs. 51±8 mg/kg/min, P< 0.1). The ratio of phosphorylated (ser307) to total insulin receptor substrate‐1, a cellular marker of insulin resistance, was greater after WD vs. NC in adipose tissue of O mice (0.99±0.1 vs. 0.75±0.1, P=0.07), but did not differ with diet in Y (P=0.4). Using two distinct methods for assessing glucose‐insulin function, our results offer strong evidence that aging increases susceptibility to WD‐induced development of insulin resistance. Impaired insulin signaling in adipose tissue may be an important mechanism underlying this effect. NIH AG013038 , AG006537 , AG015897