sir2 mutants display age-dependent obesity and fasting hyperglycemia.
Glucose (A,D), glycogen (B,E), and triglyceride (TAG) (C,F) levels were measured in control (white bars) and sir2 mutants (black bars) at one (A-C) or two (D-F) weeks of age (n = 5–15 for each group). All values are normalized to soluble protein levels. (G-H) Glucose levels were measured in control (white bars) and sir2 mutants (black bars) after an overnight fast, at one (G) or two weeks of age (H), and normalized to the number of animals (n = 37–43 for each group). An oral glucose tolerance test was performed on two (I) or three week (J) old controls (white bars) or sir2 mutants (black bars). Animals were fasted overnight, fed on 10% glucose, re-fasted for either 2 or 4 hours, and free glucose levels were measured from whole animal homogenates (n = 5–10 for each group). Although sir2 mutants do not display fasting hyperglycemia at two weeks of age in panel I, this is an exceptional result that was included because the overall profile of glucose clearance in this experiment best reflects our results from four independent replicates of this glucose tolerance test. The other three assays show fasting hyperglycemia, as depicted in panel H. Error bars are ± SEM. *p<0.05, **p<0.005, ***p<0.0005.