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Contribution of genetic and dietary insulin resistance to Alzheimer phenotype in APP/PS1 transgenic mice.

Hiltunen M, Khandelwal VK, Yaluri N, Tiilikainen T, Tusa M, Koivisto H, Krzisch M, Vepsäläinen S, Mäkinen P, Kemppainen S, Miettinen P, Haapasalo A, Soininen H, Laakso M, Tanila H - J. Cell. Mol. Med. (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. mikko.hiltunen@uef.fi

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Glucose tolerance test. Time course of B-gluc changes in (A) wild-type littermates (Aw) and (B) APdE9 transgenic (A+) female mice at 7 months of age. Corresponding changes in plasma insulin levels during the test in (C) wild-type littermates (Aw) and (D) APdE9 transgenic (A+) female mice. S: standard diet; T: typical Western diet. Mean + S.E.M.s are shown; n ∇ 4–6 mice/group.
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fig01: Glucose tolerance test. Time course of B-gluc changes in (A) wild-type littermates (Aw) and (B) APdE9 transgenic (A+) female mice at 7 months of age. Corresponding changes in plasma insulin levels during the test in (C) wild-type littermates (Aw) and (D) APdE9 transgenic (A+) female mice. S: standard diet; T: typical Western diet. Mean + S.E.M.s are shown; n ∇ 4–6 mice/group.

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).


Contribution of genetic and dietary insulin resistance to Alzheimer phenotype in APP/PS1 transgenic mice.

Hiltunen M, Khandelwal VK, Yaluri N, Tiilikainen T, Tusa M, Koivisto H, Krzisch M, Vepsäläinen S, Mäkinen P, Kemppainen S, Miettinen P, Haapasalo A, Soininen H, Laakso M, Tanila H - J. Cell. Mol. Med. (2012)

Glucose tolerance test. Time course of B-gluc changes in (A) wild-type littermates (Aw) and (B) APdE9 transgenic (A+) female mice at 7 months of age. Corresponding changes in plasma insulin levels during the test in (C) wild-type littermates (Aw) and (D) APdE9 transgenic (A+) female mice. S: standard diet; T: typical Western diet. Mean + S.E.M.s are shown; n ∇ 4–6 mice/group.
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Related In: Results  -  Collection

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fig01: Glucose tolerance test. Time course of B-gluc changes in (A) wild-type littermates (Aw) and (B) APdE9 transgenic (A+) female mice at 7 months of age. Corresponding changes in plasma insulin levels during the test in (C) wild-type littermates (Aw) and (D) APdE9 transgenic (A+) female mice. S: standard diet; T: typical Western diet. Mean + S.E.M.s are shown; n ∇ 4–6 mice/group.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland. mikko.hiltunen@uef.fi

Show MeSH
Related in: MedlinePlus