Contribution of genetic and dietary insulin resistance to Alzheimer phenotype in APP/PS1 transgenic mice.
Bottom Line: According to epidemiological studies, type-2 diabetes increases the risk of Alzheimer's disease.Neither high-fat diet nor IGF-2 increased β-amyloid burden in the brain.These findings provide evidence for new regulatory mechanisms that link type-2 diabetes and Alzheimer pathology.
Affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. firstname.lastname@example.orgShow MeSH
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Mentions: In the 7-month-old mice, the IGF-2 genotype (AwI+ or A+I+) [F(1,69) ∇ 26.0, P < 0.001] associated with elevated B-gluc levels when compared to AwIw or A+Iw mice (Fig. 1A and B). The B-gluc levels were also increased in all mice fed with TWD [F(1,69) ∇ 31.3, P < 0.001] as compared with mice on the STD (Fig. 1A and B). In addition, we observed a significant interaction with the transgenic genotype and diet. TWD did not affect B-gluc in A+ mice (A+Iw or A+I+; Fig. 1B), but it significantly elevated B-gluc in APdE9 non-transgenic (AwIw or AwI+) mice (Fig. 1A). Furthermore, the impact of the IGF-2 genotype on B-gluc levels was smaller in A+I+ than in AwI+ mice (Fig. 1A and B). GTT further revealed that both IGF-2 genotype [F(1,67) ∇ 141.0, P < 0.001] and TWD [F(1,67) ∇ 13.0, P ∇ 0.001] elevated B-gluc concentrations in Aw and A+ mice (Fig. 1A and B). The highest B-gluc levels were observed in IGF-2–positive mice on the TWD. Both factors also prolonged the elevation in B-gluc after a single i.p. injection of glucose so that at 60 min, the B-gluc levels remained the highest in IGF-2–positive mice fed with TWD when compared to the other mice [time χ IGF-2, F(3,65) ∇ 53.9, P < 0.001; time χ diet, F(3,65) ∇ 3.6, P ∇ 0.02] (Fig. 1A and B). In addition, there was a significant APdE9 χ IGF-2 [F(1,67) ∇ 6.0, P ∇ 0.02] and APdE9 χ TWD [F(1,67) ∇ 4.8, P ∇ 0.03] interaction, such that the presence of the APdE9 transgene attenuated the effects of both IGF-2 and TWD factors (Fig. 1B).
Affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. email@example.com