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
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
复制标题
DOI：
10.1111/j.1460-9568.2006.05261.x
复制
发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Hansen, Anker J.
中科院分区：
文献类型：
--
作者：
Gram, Dorte X.;Ahren, Bo;Hansen, Anker J.
郎格汉斯胰岛中调节胰岛β细胞胰岛素分泌的系统含有辣椒素敏感的抑制成分。由于表达降钙素基因相关肽(CGRP)的初级感觉神经纤维支配胰岛，且大部分含有CGRP的初级感觉神经元对辣椒素敏感，因此，支配胰岛的感觉神经纤维可能代表辣椒素敏感的抑制成分。在这里，我们研究了辣椒素受体、香草样1型瞬时受体1(TRPV1)在胰岛CGRP表达纤维中的表达，以及选择性消除辣椒素敏感的初级传入对Zucker糖尿病脂肪(ZDF)大鼠血糖稳态和胰岛素分泌下降的影响，以研究人类2型糖尿病的各个方面。我们发现在胰岛中表达CGRP的纤维也表达TRPV1。此外，我们还发现，在发生高血糖之前，全身应用辣椒素可以防止空腹、非空腹和平均24小时血糖水平的增加，以及注射后第五周评估的糖耐量的恶化。伴随这些效应的是胰岛素分泌增加和CGRP和TRPV1共表达的胰岛神经纤维几乎完全丧失。这些数据表明，胰岛中含有CGRP的纤维是辣椒素敏感的，消除这些纤维有助于防止ZDF大鼠胰岛素分泌增加而导致的血糖稳态恶化。基于这些数据，我们认为支配胰岛的辣椒素敏感纤维的活性可能在人类2型糖尿病胰岛素分泌减少的发生中起作用。
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.