Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes

Dorte X. Gram, Bo Ahrén, Istvan Nagy, Uffe B. Olsen, Christian L. Brand, Frank Sundler, René Tabanera, Ove Svendsen, Richard D. Carr, Peter Santha, Nils Wierup, Anker J. Hansen

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

The system that regulates insulin secretion from β-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component. As calcitonin gene-related peptide (CGRP)-expressing primary sensory fibers innervate the islets, and a major proportion of the CGRP-containing primary sensory neurons is sensitive to capsaicin, the islet-innervating sensory fibers may represent the capsaicin-sensitive inhibitory component. Here, we examined the expression of the capsaicin receptor, vanilloid type 1 transient receptor potential receptor (TRPV1) in CGRP-expressing fibers in the pancreatic islets, and the effect of selective elimination of capsaicin-sensitive primary afferents on the decline of glucose homeostasis and insulin secretion in Zucker diabetic fatty (ZDF) rats, which are used to study various aspects of human type 2 diabetes mellitus. We found that CGRP-expressing fibers in the pancreatic islets also express TRPV1. Furthermore, we also found that systemic capsaicin application before the development of hyperglycemia prevents the increase of fasting, non-fasting, and mean 24-h plasma glucose levels, and the deterioration of glucose tolerance assessed on the fifth week following the injection. These effects were accompanied by enhanced insulin secretion and a virtually complete loss of CGRP- and TRPV1-coexpressing islet-innervating fibers. These data indicate that CGRP-containing fibers in the islets are capsaicin sensitive, and that elimination of these fibers contributes to the prevention of the deterioration of glucose homeostasis through increased insulin secretion in ZDF rats. Based on these data we propose that the activity of islet-innervating capsaicin-sensitive fibers may have a role in the development of reduced insulin secretion in human type 2 diabetes mellitus.

Original languageEnglish
Pages (from-to)213-223
Number of pages11
JournalEuropean Journal of Neuroscience
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 1 2007

Keywords

  • CGRP
  • Low-grade inflammation
  • Primary sensory neuron
  • TRPV1

ASJC Scopus subject areas

  • Neuroscience(all)

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