Effect of amylin on memory and central insulin resistance in a rat model of Alzheimer's disease

Arch Physiol Biochem. 2020 Oct;126(4):326-334. doi: 10.1080/13813455.2018.1534244. Epub 2018 Nov 17.

Abstract

Context: Alzheimer's disease is strongly associated with brain insulin signalling.Objective: Investigating the effect of amylin as a novel treatment in streptozotocin (STZ) rat model of AD.Materials and methods: Alzheimer's disease (AD) was induced in albino rats by intracerebroventricular injection of STZ (3 mg/kg). Rats received either amylin analogue (Pramlintide 200 μg/kg/day) or Metformin (30 mg/kg/day) for 5 weeks.Results: Both Pramlintide and Metformin improve learning and memory through enhancing insulin signalling (p-IR and p-PI3K) which lead to lowering level of CSF glucose, phosphorylated tau proteins, and amyloid-β peptide (Aβ) in hippocampus.Conclusions: Insulin sensitisers as Metformin and Pramlintide can improve learning and memory and decrease the pathological changes in STZ induced rat model of AD. However, Pramlintide is superior to Metformin in some memory tests which related to its action as an amylin analogue. Amylin improves learning and memory through an independent effect other than insulin sensitisation.

Keywords: Alzheimer’s disease; Metformin; Pramlintide; amylin; insulin signalling.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Animals
  • Avoidance Learning / drug effects
  • Cognition / drug effects
  • Disease Models, Animal
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glucose / cerebrospinal fluid
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Insulin Resistance*
  • Islet Amyloid Polypeptide / blood
  • Islet Amyloid Polypeptide / pharmacology*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphorylation / drug effects
  • Rats
  • Receptor, Insulin / metabolism

Substances

  • Islet Amyloid Polypeptide
  • Phosphatidylinositol 3-Kinase
  • Receptor, Insulin
  • Glucose