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Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats

Gao, Xiang LU ; Lindqvist, Andreas LU ; Sandberg, Monica; Groop, Leif LU ; Wierup, Nils LU and Jansson, Leif (2018) In Physiological Reports 6(8).
Abstract

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion, and affects β-cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague–Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60 ng/kg*min) for 30 min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused ex vivo with GIP (10−6–10−12 mol/L) during normo- and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during... (More)

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion, and affects β-cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague–Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60 ng/kg*min) for 30 min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused ex vivo with GIP (10−6–10−12 mol/L) during normo- and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose-dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, in vivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glucose-dependent insulinotropic peptide, incretin hormones, Islet blood flow, pancreatic islets, splanchnic blood flow
in
Physiological Reports
volume
6
issue
8
publisher
John Wiley & Sons
external identifiers
  • scopus:85045986735
ISSN
2051-817X
DOI
10.14814/phy2.13685
language
English
LU publication?
yes
id
46cff87a-5d34-42a1-b154-80fc7265d8c0
date added to LUP
2018-05-04 15:56:45
date last changed
2019-01-14 07:38:44
@article{46cff87a-5d34-42a1-b154-80fc7265d8c0,
  abstract     = {<p>The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion, and affects β-cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague–Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60 ng/kg*min) for 30 min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused ex vivo with GIP (10<sup>−6</sup>–10<sup>−12</sup> mol/L) during normo- and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose-dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, in vivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators.</p>},
  articleno    = {e13685},
  author       = {Gao, Xiang and Lindqvist, Andreas and Sandberg, Monica and Groop, Leif and Wierup, Nils and Jansson, Leif},
  issn         = {2051-817X},
  keyword      = {Glucose-dependent insulinotropic peptide,incretin hormones,Islet blood flow,pancreatic islets,splanchnic blood flow},
  language     = {eng},
  month        = {04},
  number       = {8},
  publisher    = {John Wiley & Sons},
  series       = {Physiological Reports},
  title        = {Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats},
  url          = {http://dx.doi.org/10.14814/phy2.13685},
  volume       = {6},
  year         = {2018},
}