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
Autor: | Richard D. Carr, Uffe Bang Olsen, Bo Ahrén, Péter Sántha, Christian L. Brand, Nils Wierup, Ove Svendsen, Dorte Xenia Gram, Frank Sundler, René Tabanera, Anker Jon Hansen, István Nagy |
---|---|
Rok vydání: | 2007 |
Předmět: |
medicine.medical_specialty
endocrine system diseases Chemistry General Neuroscience Pancreatic islets TRPV1 Calcitonin gene-related peptide medicine.disease Insulin oscillation chemistry.chemical_compound Endocrinology medicine.anatomical_structure Capsaicin Internal medicine Diabetes mellitus medicine Glucose homeostasis lipids (amino acids peptides and proteins) Blood sugar regulation |
Zdroj: | European Journal of Neuroscience. 25:213-223 |
ISSN: | 1460-9568 0953-816X |
Popis: | The system that regulates insulin secretion from beta-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. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |