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Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats

Gram, DX; Hansen, AJ; Wilken, M; Elm, T; Svendsen, O; Carr, RD; Ahrén, Bo LU and Brand, CL (2005) In European Journal of Endocrinology 153(6). p.963-969
Abstract
Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity - and therefore might be involved in the pathophysiology - is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this. Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age)... (More)
Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity - and therefore might be involved in the pathophysiology - is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this. Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin. Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1 +/- 3.4 pmol/l in pre-obese Zucker rats vs 6.9 +/- 1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3 +/- 0.2 mmol/l vs 5.1 +/- 0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8 +/- 0.3 mmol/l vs 8.6 +/- 0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver. Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Endocrinology
volume
153
issue
6
pages
963 - 969
publisher
Society of the European Journal of Endocrinology
external identifiers
  • pmid:16322403
  • wos:000234216100028
  • scopus:29644448140
ISSN
1479-683X
DOI
10.1530/eje.1.02046
language
English
LU publication?
yes
id
a28c466a-d373-4ab4-ae6e-557f0a79f578 (old id 210561)
date added to LUP
2007-08-22 09:41:47
date last changed
2017-10-01 03:52:11
@article{a28c466a-d373-4ab4-ae6e-557f0a79f578,
  abstract     = {Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity - and therefore might be involved in the pathophysiology - is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this. Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin. Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1 +/- 3.4 pmol/l in pre-obese Zucker rats vs 6.9 +/- 1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3 +/- 0.2 mmol/l vs 5.1 +/- 0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8 +/- 0.3 mmol/l vs 8.6 +/- 0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver. Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats.},
  author       = {Gram, DX and Hansen, AJ and Wilken, M and Elm, T and Svendsen, O and Carr, RD and Ahrén, Bo and Brand, CL},
  issn         = {1479-683X},
  language     = {eng},
  number       = {6},
  pages        = {963--969},
  publisher    = {Society of the European Journal of Endocrinology},
  series       = {European Journal of Endocrinology},
  title        = {Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats},
  url          = {http://dx.doi.org/10.1530/eje.1.02046},
  volume       = {153},
  year         = {2005},
}