Type-2 Diabetes, Pancreatic Amylin, and Neuronal Metabolic Remodeling in Alzheimer's Disease

Noah Leibold, James R. Bain, Florin Despa

Research output: Contribution to journalReview articlepeer-review


Type-2 diabetes raises the risk for Alzheimer's disease (AD)-type dementia and the conversion from mild cognitive impairment to dementia, yet mechanisms connecting type-2 diabetes to AD remain largely unknown. Amylin, a pancreatic β-cell hormone co-secreted with insulin, participates in the central regulation of satiation, but also forms pancreatic amyloid in persons with type-2 diabetes and synergistically interacts with brain amyloid β (Aβ) pathology, in both sporadic and familial Alzheimer's disease (AD). Growing evidence from studies of tumor growth, together with early observations in skeletal muscle, indicates amylin as a potential trigger of cellular metabolic reprogramming. Because the blood, cerebrospinal fluid, and brain parenchyma in humans with AD have increased concentrations of amylin, amylin-mediated pathological processes in the brain may involve neuronal metabolic remodeling. This review summarizes recent progress in understanding the link between prediabetic hypersecretion of amylin and risk of neuronal metabolic remodeling and AD and suggests nutritional and medical effects of food constituents that might prevent and/or ameliorate amylin-mediated neuronal metabolic remodeling.

Original languageEnglish
JournalMolecular Nutrition and Food Research
StateAccepted/In press - 2023

Bibliographical note

Funding Information:
Funding in part by National Institutes of Health AG057290, AG053999, and NS116058 JRB would like to acknowledge the following funding resources: 5R01DK117491, 1U24DK129557, 2P30AG028716, and 1P30DK124723, and US Department of Agriculture 2020‐28640‐31521.

Publisher Copyright:
© 2023 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.


  • Alzheimer's disease
  • amylin
  • diabetes
  • metabolism
  • vascular cognitive impairment and dementia (VCID)

ASJC Scopus subject areas

  • Biotechnology
  • Food Science


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