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Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans.

Ahrén, Bo LU (2008) In Diabetologia 51(6). p.1018-1024
Abstract
AIMS/HYPOTHESIS: This study examined whether autonomic mechanisms contribute to adaptively increased insulin secretion in insulin-resistant humans, as has been proposed from studies in animals. METHODS: Insulin secretion was evaluated before and after induction of insulin resistance with or without interruption of neural transmission. Insulin resistance was induced by dexamethasone (15 mg given over 3 days) in nine healthy women (age 67 years, BMI 25.2 +/- 3.4 kg/m(2), fasting glucose 5.1 +/- 0.4 mmol/l, fasting insulin 46 +/- 6 pmol/l). Insulin secretion was evaluated as the insulin response to intravenous arginine (5 g) injected at fasting glucose and after raising glucose to 13 to15 mmol/l or to >28 mmol/l. Neural transmission across... (More)
AIMS/HYPOTHESIS: This study examined whether autonomic mechanisms contribute to adaptively increased insulin secretion in insulin-resistant humans, as has been proposed from studies in animals. METHODS: Insulin secretion was evaluated before and after induction of insulin resistance with or without interruption of neural transmission. Insulin resistance was induced by dexamethasone (15 mg given over 3 days) in nine healthy women (age 67 years, BMI 25.2 +/- 3.4 kg/m(2), fasting glucose 5.1 +/- 0.4 mmol/l, fasting insulin 46 +/- 6 pmol/l). Insulin secretion was evaluated as the insulin response to intravenous arginine (5 g) injected at fasting glucose and after raising glucose to 13 to15 mmol/l or to >28 mmol/l. Neural transmission across the ganglia was interrupted by infusion of trimethaphan (0.3-0.6 mg kg(-1) min(-1)). RESULTS: As an indication of insulin resistance, dexamethasone increased fasting insulin (to 75 +/- 8 pmol/l, p < 0.001) without significantly affecting fasting glucose. Arginine-induced insulin secretion was increased by dexamethasone at all glucose levels (by 64 +/- 12% at fasting glucose, by 80 +/- 19% at 13-15 mmol glucose and by 43 +/- 12% at >28 mmol glucose; p <0.001 for all). During dexamethasone-induced insulin resistance, trimethaphan reduced the insulin response to arginine at all three glucose levels. The augmentation of the arginine-induced insulin responses by dexamethasone-induced insulin resistance was reduced by trimethaphan by 48 +/- 6% at fasting glucose, 61 +/- 8% at 13-15 mmol/l glucose and 62 +/- 8% at >28 mmol/l glucose (p < 0.001 for all). In contrast, trimethaphan did not affect insulin secretion before dexamethasone was given. CONCLUSIONS/INTERPRETATIONS: Autonomic mechanisms contribute to the adaptative increase in insulin secretion in dexamethasone-induced insulin resistance in healthy participants. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetologia
volume
51
issue
6
pages
1018 - 1024
publisher
Springer Verlag
external identifiers
  • wos:000255537000016
  • pmid:18437349
  • scopus:43049135469
ISSN
1432-0428
DOI
10.1007/s00125-008-0995-y
language
English
LU publication?
yes
id
60d0ce88-4104-4fc3-a9bf-52c8575c607c (old id 1147041)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18437349?dopt=Abstract
date added to LUP
2008-05-06 09:17:27
date last changed
2017-10-01 04:56:48
@article{60d0ce88-4104-4fc3-a9bf-52c8575c607c,
  abstract     = {AIMS/HYPOTHESIS: This study examined whether autonomic mechanisms contribute to adaptively increased insulin secretion in insulin-resistant humans, as has been proposed from studies in animals. METHODS: Insulin secretion was evaluated before and after induction of insulin resistance with or without interruption of neural transmission. Insulin resistance was induced by dexamethasone (15 mg given over 3 days) in nine healthy women (age 67 years, BMI 25.2 +/- 3.4 kg/m(2), fasting glucose 5.1 +/- 0.4 mmol/l, fasting insulin 46 +/- 6 pmol/l). Insulin secretion was evaluated as the insulin response to intravenous arginine (5 g) injected at fasting glucose and after raising glucose to 13 to15 mmol/l or to &gt;28 mmol/l. Neural transmission across the ganglia was interrupted by infusion of trimethaphan (0.3-0.6 mg kg(-1) min(-1)). RESULTS: As an indication of insulin resistance, dexamethasone increased fasting insulin (to 75 +/- 8 pmol/l, p &lt; 0.001) without significantly affecting fasting glucose. Arginine-induced insulin secretion was increased by dexamethasone at all glucose levels (by 64 +/- 12% at fasting glucose, by 80 +/- 19% at 13-15 mmol glucose and by 43 +/- 12% at &gt;28 mmol glucose; p &lt;0.001 for all). During dexamethasone-induced insulin resistance, trimethaphan reduced the insulin response to arginine at all three glucose levels. The augmentation of the arginine-induced insulin responses by dexamethasone-induced insulin resistance was reduced by trimethaphan by 48 +/- 6% at fasting glucose, 61 +/- 8% at 13-15 mmol/l glucose and 62 +/- 8% at &gt;28 mmol/l glucose (p &lt; 0.001 for all). In contrast, trimethaphan did not affect insulin secretion before dexamethasone was given. CONCLUSIONS/INTERPRETATIONS: Autonomic mechanisms contribute to the adaptative increase in insulin secretion in dexamethasone-induced insulin resistance in healthy participants.},
  author       = {Ahrén, Bo},
  issn         = {1432-0428},
  language     = {eng},
  number       = {6},
  pages        = {1018--1024},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Evidence that autonomic mechanisms contribute to the adaptive increase in insulin secretion during dexamethasone-induced insulin resistance in humans.},
  url          = {http://dx.doi.org/10.1007/s00125-008-0995-y},
  volume       = {51},
  year         = {2008},
}