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  • Sorensen, Heidi, et al. (author)
  • Glucagon receptor knockout mice display increased insulin sensitivity and impaired beta-cell function
  • 2006
  • In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 55:12, s. 3463-3469
  • Journal article (peer-reviewed)abstract
    • In previous studies, glucagon receptor knockout mice (Gcgr(-/-)) display reduced blood glucose and increased glucose tolerance, with hyperglucagonemia and increased levels of glucagon-like peptide (GLP)-1. However, the role of glucagon receptor signaling for the regulation of islet function and insulin sensitivity is unknown. We therefore explored P-cell function and insulin sensitivity in Gcgr(-/-) and wild-type mice. The steady-state glucose infusion rate during hyperinsulinemic-euglycemic clamp was elevated in Gcgr(-/-) mice, indicating enhanced insulin sensitivity. Furthermore, the acute insulin response (AIR) to intravenous glucose was higher in Gcgr(-/-) mice. The augmented AIR to glucose was blunted by the GLP-1 receptor antagonist, exendin-3. In contrast, AIR to intravenous administration of other secretagogues was either not affected (carbachol) or significantly reduced (arginine, cholecystokinin octapeptide) in Gcgr(-/-) mice. In islets isolated from Gcgr(-/-) mice, the insulin responses to glucose and several insulin secretagogues were all significantly blunted compared with wild-type mice. Furthermore, glucose oxidation was reduced in islets from Gcgr(-/-) mice. In conclusion, the present study shows that glucagon signaling is required for normal P-cell function and that insulin action is improved when disrupting the signal. In vivo, augmented GLP-1 levels compensate for the impaired beta-cell function in Gcgr(-/-) mice.
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Type of publication
journal article (1)
Type of content
peer-reviewed (1)
Author/Editor
Ahren, Bo (1)
Sörhede-Winzell, Mar ... (1)
Fosgerau, Keld (1)
Brand, Christian L. (1)
Nishimura, Erica (1)
Sorensen, Heidi (1)
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Gelling, Richard W. (1)
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University
Lund University (1)
Language
English (1)
Research subject (UKÄ/SCB)
Medical and Health Sciences (1)
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