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Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease.

Publication ,  Journal Article
Vandal, M; White, PJ; Tremblay, C; St-Amour, I; Chevrier, G; Emond, V; Lefrançois, D; Virgili, J; Planel, E; Giguere, Y; Marette, A; Calon, F
Published in: Diabetes
December 2014

Defects in insulin production and signaling are suspected to share a key role in diabetes and Alzheimer disease (AD), two age-related pathologies. In this study, we investigated the interrelation between AD and diabetes using a high-fat diet (HFD) in a mouse model of genetically induced AD-like neuropathology (3xTg-AD). We first observed that cerebral expression of human AD transgenes led to peripheral glucose intolerance, associated with pancreatic human Aβ accumulation. High-fat diet enhanced glucose intolerance, brain soluble Aβ, and memory impairment in 3xTg-AD mice. Strikingly, a single insulin injection reversed the deleterious effects of HFD on memory and soluble Aβ levels, partly through changes in Aβ production and/or clearance. Our results are consistent with the development of a vicious cycle between AD and diabetes, potentiating both peripheral metabolic disorders and AD neuropathology. The capacity of insulin to rapidly break the deleterious effects of this cycle on soluble Aβ concentrations and memory has important therapeutic implications.

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Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

December 2014

Volume

63

Issue

12

Start / End Page

4291 / 4301

Location

United States

Related Subject Headings

  • Recognition, Psychology
  • Mice, Transgenic
  • Mice
  • Memory
  • Insulin
  • Hypoglycemic Agents
  • Humans
  • Glucose Intolerance
  • Endocrinology & Metabolism
  • Disease Models, Animal
 

Citation

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ICMJE
MLA
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Vandal, M., White, P. J., Tremblay, C., St-Amour, I., Chevrier, G., Emond, V., … Calon, F. (2014). Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease. Diabetes, 63(12), 4291–4301. https://doi.org/10.2337/db14-0375
Vandal, Milene, Phillip J. White, Cyntia Tremblay, Isabelle St-Amour, Geneviève Chevrier, Vincent Emond, Dominique Lefrançois, et al. “Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease.Diabetes 63, no. 12 (December 2014): 4291–4301. https://doi.org/10.2337/db14-0375.
Vandal M, White PJ, Tremblay C, St-Amour I, Chevrier G, Emond V, et al. Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease. Diabetes. 2014 Dec;63(12):4291–301.
Vandal, Milene, et al. “Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease.Diabetes, vol. 63, no. 12, Dec. 2014, pp. 4291–301. Pubmed, doi:10.2337/db14-0375.
Vandal M, White PJ, Tremblay C, St-Amour I, Chevrier G, Emond V, Lefrançois D, Virgili J, Planel E, Giguere Y, Marette A, Calon F. Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease. Diabetes. 2014 Dec;63(12):4291–4301.

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

December 2014

Volume

63

Issue

12

Start / End Page

4291 / 4301

Location

United States

Related Subject Headings

  • Recognition, Psychology
  • Mice, Transgenic
  • Mice
  • Memory
  • Insulin
  • Hypoglycemic Agents
  • Humans
  • Glucose Intolerance
  • Endocrinology & Metabolism
  • Disease Models, Animal