Decreased striatal vesicular monoamine transporter 2 (VMAT2) expression in a type 1 diabetic rat model: A longitudinal study using micro-PET/CT

Nucl Med Biol. 2020 Mar-Apr:82-83:89-95. doi: 10.1016/j.nucmedbio.2020.02.011. Epub 2020 Feb 19.

Abstract

Aims: Diabetes mellitus is a risk factor for Parkinson's disease. These diseases share similar pathogenic pathways, such as mitochondrial dysfunction, inflammation, and altered metabolism. Despite these similarities, the pathogenic relationship between these two diseases is unclear. [18F]FP-(+)-DTBZ is a promising radiotracer targeting VMAT2, which has been used to measure β-cell mass and to diagnose Parkinson's disease. The aim of this study was to examine the effect of type 1 diabetes on VMAT2 expression in the striatum using [18F]FP-(+)-DTBZ.

Materials and methods: A longitudinal study of type 1 diabetic rats was established by intraperitoneally injecting male Wistar rats with streptozotocin. Rats injected with saline were used as the control group. Glucose level, body weight, and [18F]FP-(+)-DTBZ uptake in the striatum and pancreas were evaluated at 0.5, 1, 4, 6 and 12 months after STZ or saline injection.

Results: At one-half month post-STZ injection, the glucose levels in these rats increased and then returned to a normal level at 6 months. Along with increased glucose levels, body weight was also decreased significantly and returned slowly to a normal level. β-Cell mass and striatal [18F]FP-(+)-DTBZ uptake were impaired significantly at 2 weeks post-STZ injection in type 1 diabetic rats and returned to a normal level at 6 and 4 months post-STZ injection.

Conclusions: Due to increased glucose levels and decreased β-cell mass, decreased [18F]FP-(+)-DTBZ uptake in the striatum was observed in type 1 diabetic rats. Decreased BCM and increased glucose levels were correlated with VMAT2 expression in the striatum which indicated DM is a risk factor for PD.

Keywords: Diabetes; Pancreas; Parkinson's disease; VMAT2; β-Cell mass.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnostic imaging*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Longitudinal Studies
  • Male
  • Neostriatum / diagnostic imaging*
  • Neostriatum / metabolism*
  • Positron Emission Tomography Computed Tomography*
  • Rats
  • Rats, Wistar
  • Vesicular Monoamine Transport Proteins / metabolism*

Substances

  • Blood Glucose
  • Slc18a2 protein, rat
  • Vesicular Monoamine Transport Proteins