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Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice.

Gunnarsson, Thomas LU ; Sörhede Winzell, Maria LU ; Deacon, Carolyn F; Larsen, Marianne O; Jelic, Katarina; Carr, Richard D and Ahrén, Bo LU (2006) In Endocrinology 147(7). p.3173-3180
Abstract
Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins, especially whey protein (WP), have insulinotropic effects and can reduce postprandial glycemia. This effect may involve the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). To explore this, we examined the release and inactivation of GIP and GLP-1 after administration of glucose with or without OA or WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold augmented by addition of WP (75 mg; P < 0.01), which was associated with enhanced oral glucose tolerance (P < 0.01). The insulin response to glucose was also augmented by addition of OA (34 mg; P... (More)
Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins, especially whey protein (WP), have insulinotropic effects and can reduce postprandial glycemia. This effect may involve the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). To explore this, we examined the release and inactivation of GIP and GLP-1 after administration of glucose with or without OA or WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold augmented by addition of WP (75 mg; P < 0.01), which was associated with enhanced oral glucose tolerance (P < 0.01). The insulin response to glucose was also augmented by addition of OA (34 mg; P < 0.05) although only 1.5-fold and with no associated increase in glucose elimination. The slope of the glucose-insulin curve was increased by OA (1.7-fold; P < 0.05) and by WP(4-fold; P < 0.01) compared with glucose alone, suggesting potentiation of glucose-stimulated insulin release. WP increased GLP-1 secretion (P < 0.01), whereas GIP secretion was unaffected. OA did not affect GIP or GLP-1 secretion. Nevertheless, WP increased the levels of both intact GIP and intact GLP-1 (both P < 0.01), and OA increased the levels of intact GLP-1 (P < 0.05). WP inhibited dipeptidyl peptidase IV activity in the proximal small intestine by 50% (P < 0.05), suggesting that luminal degradation of WP generates small fragments, which are substrates for dipeptidyl peptidase IV and act as competitive inhibitors. We therefore conclude that fat and protein may serve as exogenous regulators of secretion and inactivation of the incretin hormones with beneficial influences on glucose metabolism. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Endocrinology
volume
147
issue
7
pages
3173 - 3180
publisher
Endocrine Society
external identifiers
  • wos:000238312400002
  • pmid:16627575
  • scopus:33745137900
ISSN
0013-7227
DOI
10.1210/en.2005-1442
language
English
LU publication?
yes
id
d4202cbb-95e5-47dc-b189-53e23fdaac1a (old id 155819)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16627575&dopt=Abstract
date added to LUP
2007-07-09 15:37:34
date last changed
2019-07-02 02:02:51
@article{d4202cbb-95e5-47dc-b189-53e23fdaac1a,
  abstract     = {Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins, especially whey protein (WP), have insulinotropic effects and can reduce postprandial glycemia. This effect may involve the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). To explore this, we examined the release and inactivation of GIP and GLP-1 after administration of glucose with or without OA or WP through gastric gavage in anesthetized C57BL/6J mice. Insulin responses to glucose (75 mg) were 3-fold augmented by addition of WP (75 mg; P &lt; 0.01), which was associated with enhanced oral glucose tolerance (P &lt; 0.01). The insulin response to glucose was also augmented by addition of OA (34 mg; P &lt; 0.05) although only 1.5-fold and with no associated increase in glucose elimination. The slope of the glucose-insulin curve was increased by OA (1.7-fold; P &lt; 0.05) and by WP(4-fold; P &lt; 0.01) compared with glucose alone, suggesting potentiation of glucose-stimulated insulin release. WP increased GLP-1 secretion (P &lt; 0.01), whereas GIP secretion was unaffected. OA did not affect GIP or GLP-1 secretion. Nevertheless, WP increased the levels of both intact GIP and intact GLP-1 (both P &lt; 0.01), and OA increased the levels of intact GLP-1 (P &lt; 0.05). WP inhibited dipeptidyl peptidase IV activity in the proximal small intestine by 50% (P &lt; 0.05), suggesting that luminal degradation of WP generates small fragments, which are substrates for dipeptidyl peptidase IV and act as competitive inhibitors. We therefore conclude that fat and protein may serve as exogenous regulators of secretion and inactivation of the incretin hormones with beneficial influences on glucose metabolism.},
  author       = {Gunnarsson, Thomas and Sörhede Winzell, Maria and Deacon, Carolyn F and Larsen, Marianne O and Jelic, Katarina and Carr, Richard D and Ahrén, Bo},
  issn         = {0013-7227},
  language     = {eng},
  number       = {7},
  pages        = {3173--3180},
  publisher    = {Endocrine Society},
  series       = {Endocrinology},
  title        = {Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice.},
  url          = {http://dx.doi.org/10.1210/en.2005-1442},
  volume       = {147},
  year         = {2006},
}