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The augmenting effect on insulin secretion by oral versus intravenous glucose is exaggerated by high-fat diet in mice.

Ahrén, Bo LU ; Sörhede Winzell, Maria LU and Pacini, Giovanni (2008) In Journal of Endocrinology 197(1). p.181-187
Abstract
To study whether the incretin effect is involved in adaptively increased insulin secretion in insulin resistance, glucose was infused at a variable rate to match glucose levels after oral glucose (25 mg) in normal anesthetized C57BL/6J female mice or in mice rendered insulin resistant by 8 weeks of high-fat feeding. Insulin response was markedly higher after oral than i.v. glucose in both groups, and this augmentation was even higher in high-fat fed than normal mice. In normal mice, the area under the curve (AUC(insulin)) was augmented from 4.0+/-0.8 to 8.0+/-1.8 nmol/lx60 min by the oral glucose, i.e. by a factor of 2 (P=0.023), whereas in the high-fat fed mice, AUC(insulin) was augmented from 0.70+/-0.4 to 12.4+/-2.5 nmol/lx60 min, i.e.... (More)
To study whether the incretin effect is involved in adaptively increased insulin secretion in insulin resistance, glucose was infused at a variable rate to match glucose levels after oral glucose (25 mg) in normal anesthetized C57BL/6J female mice or in mice rendered insulin resistant by 8 weeks of high-fat feeding. Insulin response was markedly higher after oral than i.v. glucose in both groups, and this augmentation was even higher in high-fat fed than normal mice. In normal mice, the area under the curve (AUC(insulin)) was augmented from 4.0+/-0.8 to 8.0+/-1.8 nmol/lx60 min by the oral glucose, i.e. by a factor of 2 (P=0.023), whereas in the high-fat fed mice, AUC(insulin) was augmented from 0.70+/-0.4 to 12.4+/-2.5 nmol/lx60 min, i.e. by a factor of 17 (P<0.001). To examine whether the incretin hormone glucagon-like peptide-1 (GLP-1) is responsible for this difference, the effect of i.v. GLP-1 was compared in normal and high-fat fed mice. The sensitivity to i.v. GLP-1 in stimulating insulin secretion was increased in the high-fat diet fed mice: the lowest effective dose of GLP-1 was 650 pmol/kg in normal mice and 13 pmol/kg in the high-fat diet fed mice. We conclude that 1) the incretin effect contributes by approximately 50% to insulin secretion by the oral glucose in normal mice, 2) this effect is markedly exaggerated in insulin-resistant mice fed a high-fat diet, and 3) this augmented incretin contribution in the high-fat fed mice may partially be explained by GLP-1. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Endocrinology
volume
197
issue
1
pages
181 - 187
publisher
Society for Endocrinology
external identifiers
  • pmid:18372244
  • wos:000255187900018
  • scopus:42449098132
ISSN
1479-6805
DOI
10.1677/JOE-07-0460
language
English
LU publication?
yes
id
66024b41-4c7a-4f17-ba71-dd38717f526b (old id 1052037)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18372244?dopt=Abstract
date added to LUP
2008-04-01 08:26:52
date last changed
2017-01-01 07:34:22
@article{66024b41-4c7a-4f17-ba71-dd38717f526b,
  abstract     = {To study whether the incretin effect is involved in adaptively increased insulin secretion in insulin resistance, glucose was infused at a variable rate to match glucose levels after oral glucose (25 mg) in normal anesthetized C57BL/6J female mice or in mice rendered insulin resistant by 8 weeks of high-fat feeding. Insulin response was markedly higher after oral than i.v. glucose in both groups, and this augmentation was even higher in high-fat fed than normal mice. In normal mice, the area under the curve (AUC(insulin)) was augmented from 4.0+/-0.8 to 8.0+/-1.8 nmol/lx60 min by the oral glucose, i.e. by a factor of 2 (P=0.023), whereas in the high-fat fed mice, AUC(insulin) was augmented from 0.70+/-0.4 to 12.4+/-2.5 nmol/lx60 min, i.e. by a factor of 17 (P&lt;0.001). To examine whether the incretin hormone glucagon-like peptide-1 (GLP-1) is responsible for this difference, the effect of i.v. GLP-1 was compared in normal and high-fat fed mice. The sensitivity to i.v. GLP-1 in stimulating insulin secretion was increased in the high-fat diet fed mice: the lowest effective dose of GLP-1 was 650 pmol/kg in normal mice and 13 pmol/kg in the high-fat diet fed mice. We conclude that 1) the incretin effect contributes by approximately 50% to insulin secretion by the oral glucose in normal mice, 2) this effect is markedly exaggerated in insulin-resistant mice fed a high-fat diet, and 3) this augmented incretin contribution in the high-fat fed mice may partially be explained by GLP-1.},
  author       = {Ahrén, Bo and Sörhede Winzell, Maria and Pacini, Giovanni},
  issn         = {1479-6805},
  language     = {eng},
  number       = {1},
  pages        = {181--187},
  publisher    = {Society for Endocrinology},
  series       = {Journal of Endocrinology},
  title        = {The augmenting effect on insulin secretion by oral versus intravenous glucose is exaggerated by high-fat diet in mice.},
  url          = {http://dx.doi.org/10.1677/JOE-07-0460},
  volume       = {197},
  year         = {2008},
}