Figure 4.

SNCA mice are resistant to high calorie diet-induced insulin resistance. At 12 weeks of age, both SNCA and WT littermates on the control diet displayed normal responses to a glucose bolus, including a rise in glucose and insulin followed by a fall in both with a return to baseline glucose levels by 120 minutes (A&B). At 36 weeks of age, both strains receiving the control diet displayed an increase in glucose and insulin with a return to normal glucose levels, however glucose levels fell more slowly in wild-type mice than in SNCA littermates; blood glucose levels remained significantly elevated over SNCA at 30 and 60 minutes after the bolus injection (p<0.009) (C). Insulin levels in 36 week old mice on the control diet were comparable between the two strains during the whole tolerance test (D). At 36 weeks of age after 24 weeks on a HCD, wild-type mice displayed significantly greater blood glucose levels compared to SNCA at 30, 90 and 120 mins after gavage, indicating an impaired ability to return to normal baseline glucose levels (p<0.028) (E). More strikingly, plasma insulin levels were drastically higher in wild-type mice than in SNCA mice after 12 weeks on a HCD; these differences were significant at all time points tested (p<0.0014) (F). Calculations for the area under the curve (AUC) for the glucose and insulin response curves shown in A–F further demonstrate both alterations in glucose and insulin regulation after a HCD and differences between SNCA and WT littermates (G&H).