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Sensory nerve inactivation by resiniferatoxin improves insulin sensitivity in male obese Zucker rats

Moesgaard, S G; Brand, C L; Sturis, J; Ahrén, Bo LU ; Wilken, M; Fleckner, J; Carr, R D; Svendsen, O; Hansen, A J and Gram, D X (2005) In American Journal of Physiology: Endocrinology and Metabolism 288(6). p.1137-1145
Abstract
Recent studies have suggested that sensory nerves may influence insulin secretion and action. The present study investigated the effects of resiniferatoxin (RTX) inactivation of sensory nerves ( desensitization) on oral glucose tolerance, insulin secretion and whole body insulin sensitivity in the glucose intolerant, hyperinsulinemic, and insulin-resistant obese Zucker rat. After RTX treatment (0.05 mg/kg RTX sc given at ages 8, 10, and 12 wk), fasting plasma insulin was reduced ( P < 0.0005), and oral glucose tolerance was improved ( P < 0.005). Pancreas perfusion showed that baseline insulin secretion ( 7 mM glucose) was lower in RTX-treated rats ( P = 0.01). Insulin secretory responsiveness to 20 mM glucose was enhanced in the... (More)
Recent studies have suggested that sensory nerves may influence insulin secretion and action. The present study investigated the effects of resiniferatoxin (RTX) inactivation of sensory nerves ( desensitization) on oral glucose tolerance, insulin secretion and whole body insulin sensitivity in the glucose intolerant, hyperinsulinemic, and insulin-resistant obese Zucker rat. After RTX treatment (0.05 mg/kg RTX sc given at ages 8, 10, and 12 wk), fasting plasma insulin was reduced ( P < 0.0005), and oral glucose tolerance was improved ( P < 0.005). Pancreas perfusion showed that baseline insulin secretion ( 7 mM glucose) was lower in RTX-treated rats ( P = 0.01). Insulin secretory responsiveness to 20 mM glucose was enhanced in the perfused pancreas of RTX-treated rats ( P < 0.005) but unaffected in stimulated, isolated pancreatic islets. At the peak of spontaneous insulin resistance in the obese Zucker rat, insulin sensitivity was substantially improved after RTX treatment, as evidenced by higher glucose infusion rates (GIR) required to maintain euglycemia during a hyperinsulinemic euglycemic ( 5 mU center dot kg(-1) center dot min(-1)) clamp (GIR(60 - 120min): 5.97 +/- 0.62 vs. 11.65 +/- 0.83 mg center dot kg(-1) center dot min(-1) in RTX-treated rats, P = 0.003). In conclusion, RTX treatment and, hence, sensory nerve desensitization of adult male obese Zucker rats improved oral glucose tolerance by enhancing insulin secretion, and, in particular, by improving insulin sensitivity. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
capsaicin, hyperinsulinemic euglycemic clamp, obesity
in
American Journal of Physiology: Endocrinology and Metabolism
volume
288
issue
6
pages
1137 - 1145
publisher
American Physiological Society
external identifiers
  • wos:000229308000011
  • pmid:15883192
  • scopus:21144438021
ISSN
1522-1555
DOI
10.1152/ajpendo.00356.2004
language
English
LU publication?
yes
id
bed33aab-3acc-4b7b-85d2-7c97c6c4ab48 (old id 239196)
date added to LUP
2007-10-05 09:32:29
date last changed
2017-07-02 04:29:24
@article{bed33aab-3acc-4b7b-85d2-7c97c6c4ab48,
  abstract     = {Recent studies have suggested that sensory nerves may influence insulin secretion and action. The present study investigated the effects of resiniferatoxin (RTX) inactivation of sensory nerves ( desensitization) on oral glucose tolerance, insulin secretion and whole body insulin sensitivity in the glucose intolerant, hyperinsulinemic, and insulin-resistant obese Zucker rat. After RTX treatment (0.05 mg/kg RTX sc given at ages 8, 10, and 12 wk), fasting plasma insulin was reduced ( P &lt; 0.0005), and oral glucose tolerance was improved ( P &lt; 0.005). Pancreas perfusion showed that baseline insulin secretion ( 7 mM glucose) was lower in RTX-treated rats ( P = 0.01). Insulin secretory responsiveness to 20 mM glucose was enhanced in the perfused pancreas of RTX-treated rats ( P &lt; 0.005) but unaffected in stimulated, isolated pancreatic islets. At the peak of spontaneous insulin resistance in the obese Zucker rat, insulin sensitivity was substantially improved after RTX treatment, as evidenced by higher glucose infusion rates (GIR) required to maintain euglycemia during a hyperinsulinemic euglycemic ( 5 mU center dot kg(-1) center dot min(-1)) clamp (GIR(60 - 120min): 5.97 +/- 0.62 vs. 11.65 +/- 0.83 mg center dot kg(-1) center dot min(-1) in RTX-treated rats, P = 0.003). In conclusion, RTX treatment and, hence, sensory nerve desensitization of adult male obese Zucker rats improved oral glucose tolerance by enhancing insulin secretion, and, in particular, by improving insulin sensitivity.},
  author       = {Moesgaard, S G and Brand, C L and Sturis, J and Ahrén, Bo and Wilken, M and Fleckner, J and Carr, R D and Svendsen, O and Hansen, A J and Gram, D X},
  issn         = {1522-1555},
  keyword      = {capsaicin,hyperinsulinemic euglycemic clamp,obesity},
  language     = {eng},
  number       = {6},
  pages        = {1137--1145},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Endocrinology and Metabolism},
  title        = {Sensory nerve inactivation by resiniferatoxin improves insulin sensitivity in male obese Zucker rats},
  url          = {http://dx.doi.org/10.1152/ajpendo.00356.2004},
  volume       = {288},
  year         = {2005},
}